大黄鱼两种半胱氨酸蛋白酶抑制剂的分子特征与功能研究
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摘要
Cystatin是一类与半胱氨酸蛋白酶紧密结合的、可逆的天然抑制剂。因为这些半胱氨酸蛋白酶存在于所有生物体内,并参与多种生物学、病理学过程,所以cystatin对这些蛋白酶的功能调节尤其重要。在免疫系统中,cystatin可调节组织蛋白酶活性和抗原提呈,诱导TNFα和IL-10的合成,并且刺激IFN-γ激活的鼠巨噬细胞产生NO。我们在前期研究中,建立了一个poLyI:C诱导大黄鱼脾脏SmartcDNA文库,从中发现了两个编码不同半胱氨酸蛋白酶抑制剂的EST克隆,经测序比对后确定为大黄鱼stefin和cystatin类似物,同属于cystatin家族。
本文首先克隆了1个大黄鱼cystatin全长cDNA。序列分析结果表明,大黄鱼cystatin全长cDNA包括688个核苷酸,编码一个118个氨基酸的蛋白,分子量13kDa,推测其具有一个由21个氨基酸组成的信号肽序列。分别与鱼类、高等脊椎动物和线虫类有27.1-45.9%,30.0-31.7%和16.3-30.6%的序列一致性,其中与pufferfish的序列一致性最高,为45.9%。与人的cystatin C有30.8%的序列一致性,与鸡蛋白cystatin有31.7%的序列一致性。大黄鱼cystatin也含有典型的cystatin家族保守结构域GLy-GLy(25,26),QLVAG(69-73)和PW(106-107)。四个半胱氨酸残基,分别为C~(56)、C~(87)、C~(98)和C~(118)。可能形成两对二硫键,维持其独特的空间结构。但大黄鱼的四个半胱氨酸残基中只有3个是与其它物种的位置是一致,另有一个半胱氨酸残基(C~(56))向N-端偏移,这有可能影响其空间结构的形成。另外,大黄鱼的cystatin蛋白氨基酸序列中也有S~(52)N~(53)残基,可能是抑制Legumain的活性位点。基因组分析表明,大黄鱼cystatin基因由3上外显子和2个内含子组成,与人、小鼠和斑马鱼的cystatin基因组结构基本一致。RT-PCR分析表明该基因在肠、鳃、心、肌、脾、肝、血和肾中为组成型表达,在脾和肾中的基因转录水平最高,在鳃、肌肉和血中最低。分别用三联灭活细菌疫苗或poLy(I:C)刺激后,该基因的mRNA水平在肾和脾中上调,在血中下调,但下调幅度不大。用pGEX-4T-2原核表达载体构建了大黄鱼cystatin(GST)重组表达载体,表达并纯化了重组Lyccys(GST)融合蛋白。以酪蛋白为底物,检测了该融合蛋白对papain的抑制比活力为40个抑制活力单位。用胶体金免疫标记电镜技术研究了大黄鱼cystatin蛋白在肾、脾组织的细胞内的定位情况。经检测表明,该蛋白主要分布在细胞质中,并附着于粗面内质网(rER),在胞内泡状结构(如内质体或溶酶体)内有较多,细胞核内没有发现。用相对定量荧光PCR检测重组大黄鱼cystatin对免疫免疫相关基因TNF-α2和IL-10的转录水平的调节作用。结果是大黄鱼cystatin能刺激大黄鱼脾和肾中TNF-α2和IL-10 mRNA水平的上调。因此认为大黄鱼cystatin可能具有与哺乳动物cystatin相似的免疫调节功能。
同时,我们也克隆了1个大黄鱼stefin全长cDNA,包含556个核苷酸,编码一个99个氨基酸组成的蛋白,分子量约11kDa。分别与纯、牛、河豚、猪、虹鳟和斑马鱼的stefin蛋白有47.5%,47.5%,46.1%,42.7%,38.0%,38.0%的序列同源性。与人和小鼠的stefin A和B蛋白分别有43.0%和38.0%,38.4%和32.0%的一致性。编码的蛋白具有stefin家族的特征结构域,即N-末端的GLy~6-GLy~7作用位点和一保守的QLVAG(48-51)motif。基因组分析表明,大黄鱼stefin基因由3个外显子和2内含子组成,与人、小鼠和斑马鱼的stefin基因组结构基本一致。RT-PCR分析表明该基因在肠、鳃、心、肌、脾、肝、血和肾中均有表达,其中在血和肾中的基因转录水平最高,在肠中最低。分别用三联灭活细菌疫苗或poLy(I:C)刺激后,该基因的mRNA水平在肾和脾中上调,在血中下调。用pGEX-4T-2原核表达载体构建了大黄鱼stefin(GST)(Lycstefin(GST))重组表达载体,表达并纯化出有活性的Lycstefin(GST)融合蛋白。以酪蛋白为底物,检测了该融合蛋白对papain的抑制比活力为42个抑制活力单位。用相对定量荧光PCR检测重组大黄鱼stefin对免疫相关基因TNF-α2和IL-10的转录水平的调节作用。结果是大黄鱼stefin没有引起大黄鱼脾和肾中TNF-α2和IL-10 mRNA水平的变化。用免疫电镜技术研究了大黄鱼stefin蛋白在肾、脾组织的细胞内的定位情况。经检测表明,该蛋白主要散布在细胞质中,并不附着于粗面内质网(rER),在细胞核和胞内泡状结构(如内质体或溶酶体)内有少量分布。
Cystatins are natuaL tight-binding reversibLe inhibitors of cysteine proteases. Because these cysteine proteases exist in aLL Living organisms and because they are invoLved in various bioLogicaL and pathoLogicaL processes, the controL of these protease functions by cystatins is of cardinaL importance. In the immune system, cystatins moduLate cathepsin activities and antigen presentation. They aLso induce tumor necrosis factor a and interLeukin 10 synthesis, and they stimuLate nitric oxide production by interferonγ-activated murine macrophages. A spLeen cDNA Library of Large yeLLow croaker was constructed by induction with poLyI:C. There were two reLative cysteine proteases inhibitors found in tow cLones respectivLy, which were characterized to the members of the cystatin superfamiLy, after being sequenced and bLasted. Three immune reLative gene homoLogues of Large yeLLow croaker were cLoned from the spLeen of Large yeLLow croaker, which were tumor necrosis factorα1(TNF-α1), tumor necrosis factorα2(TNF-α2) and interLeukin 10(IL-10) homoLogue respectiveLy.
In the present study, it was reported that a cLoning from the spLeen cDNA Library from the Large yeLLow croaker is a cystatin homoLogue(Lyccys), with 688 nucLeotides (nt) encoding a protein of 118 amino acids (aa) with a 21aa signaL peptide, 13kDa. The deduced protein shared 27.1-45.9 % , 30.0-31.7 %和16.3-30.6% sequence identity to the sequences found in other fishes, some high vertebrates and some nematodes. The highest sequence identity of 45.9% was achieved by Lyccys and a cystatin from pufferfish. It shared 30.8%, 31.7% sequence identity to the sequences of human cystatin C and chicken egg white cystatin. The Lyccys contains typicaL conserved motifs of cystatin superfamiLy, a N-terminaL GLy-GLy (25, 26), QLVAG (69-73) and a C-terminaL PW (106-107) known to interact with the active site of famiLy Cl cysteine peptidases. There was a conserved S~(52)N~(53) which may be the reactive site of Legumain, a cysteine endopeptidase causing Limited proteoLysis of precursor proteins and protein spLicing. It had the structuraL arrangement of four conserved cysteine residues (C~(56), C~(87), C~(98) and C~(118)) with two disuLphide bonds towards the carboxyL terminusas found in Large known cystatins, however there is a cysteine residue (C~(56)) in the different Location from the others, which was removed to N-terminus. This maybe affected the space structure and its bioLogicaL functions. The genomic DNA sequence of Lyccys was cLoned and sequenced, constituting of three exons and two introns, sharing the simiLar genomic structure with human cystatin C, mouse cystatin C and zebrafish cystatin. Tissue expression profiLe anaLysis with reverse transcription-PCR showed that Lyccys gene was constitutiveLy expressed in aLL eight tissues (intestine, giLL, heart, muscLe, spLeen, Liver, bLood and kidney) examined, aLthough at a different LeveL. The highest LeveL of Lycstefm mRNA was detected in spLeen and kidney, and the Lowest in giLL, muscLe and bLood. The transcript LeveL of Lyccys was increased in kidney and spLeen, but decreased in bLood after induction with poLyI:C or inactivated trivaLent bacteriaL vaccine, anaLysis by reLative quantitative reaL-time PCR. The recombinant Lyccys(GST) (rLyccys(GST)) was expressed in E.coLi BL-21, and purified. The inhibitory specific activity of rLyccys(GST) against papain with the substrate casein was detected to be 40 U/mg. The intraceLLuLar LocaLization of Lyccys in kidney and spLeen ceLLs with immune coLLoidaL goLd eLectron microscopy was suggested that Lyccys was onLy distributed in cytopLasm, mainLy attached to rough endopLasmic reticuLum(rER), Large in vesicLes (endosome or Lysosome), not found in nucLeues. The transcript LeveLs of TNF-α2 and IL-10 were increased in kidney and spLeen of Large yeLLow croaker by injection with rLyccys(GST) through reLative quantitative reaL-time PCR. It is specuLated that the cystatin homoLogue of Large yeLLow croaker probabLy pLay a cardinaL immunomoduLatory roLe simiLar to that of mammaLs.
On the other hand, we reported the cLoning of a stefin gene homoLogue from the spLeen cDNA Library of Large yeLLow croaker (Pseudosciana crocea), an economicaLLy important marine fish (Lycstefm). The fuLL Length cDNA of Lycstefm is 556 nucLeotides (nt) encoding a protein of 99 amino acids (aa0, with a putative moLecuLar weight of 11 kDa. The deduced protein shares 47.5%,47.5%,46.1%, 42.7%,38.0%,38.0% sequence identity to the sequences found in pufferfish, cattLe, takifugu, pig, rainbow trout and zebrafish, respectiveLy; and 43.0%和P 38.0%, 38.4%和 32.0% sequence identity to the sequences of human stefin A, human stefin B, mouse stefin A and mouse stefin B respectiveLy. The deduced Lycstefin contains conserved activation LocaLization of N-terminaL GLy~6-GLy~7 ,a conserved QLVAG (48-51) motif, which were found in aLL stefins. The Lycstefin genomic DNA sequence was cLoned and sequenced, constituting of three exons and two introns, sharing the simiLar genomic structure with human stefin A, mouse stefin A and zebrafish cystatin B. Tissue expression profiLe anaLysis with reverse transcription-PCR (RT-PCR) showed that Lycstefin gene was constitutiveLy expressed in aLL eight tissues (intestine, giLL, heart, muscLe, spLeen, Liver, bLood and kidney) examined, aLthough at a different LeveL. The highest LeveL of Lycstefin mRNA was detected in bLood and kidney, and the Lowest in intestine. The transcript LeveL of Lycstefin was increased in kidney and spLeen , but decreased in bLood after induction with poLyI:C or inactivated trivaLent bacteriaL vaccine, anaLysis by reLative quantitative reaL-time PCR. The recombinant Lycstefin(GST) (rLycstefin(GST)) was expressed in E.coLi BL-21, and purified. The inhibitory specific activity of rLycstefin(GST) against papain with the substrate caseins was detected to be 42 U/mg. The intraceLLuLar LocaLization of Lycstefin in kidney and spLeen with immune coLLoidaL goLd eLectron microscopy was suggested that Lycstefin was mainLy distributed diffuseLy throughout the cytopLasm, and not attached to rough endopLasmic reticuLum(rER) . LittLe was found in nucLeues and vesicLes (endosome or Lysosome). The transcript LeveLs of TNF-α2 and IL-10 were not changed in kidney and spLeen of Large yeLLow croaker by injection with rLyccys(GST) through reLative quantitative reaL-time PCR. So it is suggested that the stefin homoLogue of Large yeLLow croaker couLdn't moduLate The transcript LeveLs of TNF-α2 and IL-10.
本文首先克隆了1个大黄鱼cystatin全长cDNA。序列分析结果表明,大黄鱼cystatin全长cDNA包括688个核苷酸,编码一个118个氨基酸的蛋白,分子量13kDa,推测其具有一个由21个氨基酸组成的信号肽序列。分别与鱼类、高等脊椎动物和线虫类有27.1-45.9%,30.0-31.7%和16.3-30.6%的序列一致性,其中与pufferfish的序列一致性最高,为45.9%。与人的cystatin C有30.8%的序列一致性,与鸡蛋白cystatin有31.7%的序列一致性。大黄鱼cystatin也含有典型的cystatin家族保守结构域GLy-GLy(25,26),QLVAG(69-73)和PW(106-107)。四个半胱氨酸残基,分别为C~(56)、C~(87)、C~(98)和C~(118)。可能形成两对二硫键,维持其独特的空间结构。但大黄鱼的四个半胱氨酸残基中只有3个是与其它物种的位置是一致,另有一个半胱氨酸残基(C~(56))向N-端偏移,这有可能影响其空间结构的形成。另外,大黄鱼的cystatin蛋白氨基酸序列中也有S~(52)N~(53)残基,可能是抑制Legumain的活性位点。基因组分析表明,大黄鱼cystatin基因由3上外显子和2个内含子组成,与人、小鼠和斑马鱼的cystatin基因组结构基本一致。RT-PCR分析表明该基因在肠、鳃、心、肌、脾、肝、血和肾中为组成型表达,在脾和肾中的基因转录水平最高,在鳃、肌肉和血中最低。分别用三联灭活细菌疫苗或poLy(I:C)刺激后,该基因的mRNA水平在肾和脾中上调,在血中下调,但下调幅度不大。用pGEX-4T-2原核表达载体构建了大黄鱼cystatin(GST)重组表达载体,表达并纯化了重组Lyccys(GST)融合蛋白。以酪蛋白为底物,检测了该融合蛋白对papain的抑制比活力为40个抑制活力单位。用胶体金免疫标记电镜技术研究了大黄鱼cystatin蛋白在肾、脾组织的细胞内的定位情况。经检测表明,该蛋白主要分布在细胞质中,并附着于粗面内质网(rER),在胞内泡状结构(如内质体或溶酶体)内有较多,细胞核内没有发现。用相对定量荧光PCR检测重组大黄鱼cystatin对免疫免疫相关基因TNF-α2和IL-10的转录水平的调节作用。结果是大黄鱼cystatin能刺激大黄鱼脾和肾中TNF-α2和IL-10 mRNA水平的上调。因此认为大黄鱼cystatin可能具有与哺乳动物cystatin相似的免疫调节功能。
同时,我们也克隆了1个大黄鱼stefin全长cDNA,包含556个核苷酸,编码一个99个氨基酸组成的蛋白,分子量约11kDa。分别与纯、牛、河豚、猪、虹鳟和斑马鱼的stefin蛋白有47.5%,47.5%,46.1%,42.7%,38.0%,38.0%的序列同源性。与人和小鼠的stefin A和B蛋白分别有43.0%和38.0%,38.4%和32.0%的一致性。编码的蛋白具有stefin家族的特征结构域,即N-末端的GLy~6-GLy~7作用位点和一保守的QLVAG(48-51)motif。基因组分析表明,大黄鱼stefin基因由3个外显子和2内含子组成,与人、小鼠和斑马鱼的stefin基因组结构基本一致。RT-PCR分析表明该基因在肠、鳃、心、肌、脾、肝、血和肾中均有表达,其中在血和肾中的基因转录水平最高,在肠中最低。分别用三联灭活细菌疫苗或poLy(I:C)刺激后,该基因的mRNA水平在肾和脾中上调,在血中下调。用pGEX-4T-2原核表达载体构建了大黄鱼stefin(GST)(Lycstefin(GST))重组表达载体,表达并纯化出有活性的Lycstefin(GST)融合蛋白。以酪蛋白为底物,检测了该融合蛋白对papain的抑制比活力为42个抑制活力单位。用相对定量荧光PCR检测重组大黄鱼stefin对免疫相关基因TNF-α2和IL-10的转录水平的调节作用。结果是大黄鱼stefin没有引起大黄鱼脾和肾中TNF-α2和IL-10 mRNA水平的变化。用免疫电镜技术研究了大黄鱼stefin蛋白在肾、脾组织的细胞内的定位情况。经检测表明,该蛋白主要散布在细胞质中,并不附着于粗面内质网(rER),在细胞核和胞内泡状结构(如内质体或溶酶体)内有少量分布。
Cystatins are natuaL tight-binding reversibLe inhibitors of cysteine proteases. Because these cysteine proteases exist in aLL Living organisms and because they are invoLved in various bioLogicaL and pathoLogicaL processes, the controL of these protease functions by cystatins is of cardinaL importance. In the immune system, cystatins moduLate cathepsin activities and antigen presentation. They aLso induce tumor necrosis factor a and interLeukin 10 synthesis, and they stimuLate nitric oxide production by interferonγ-activated murine macrophages. A spLeen cDNA Library of Large yeLLow croaker was constructed by induction with poLyI:C. There were two reLative cysteine proteases inhibitors found in tow cLones respectivLy, which were characterized to the members of the cystatin superfamiLy, after being sequenced and bLasted. Three immune reLative gene homoLogues of Large yeLLow croaker were cLoned from the spLeen of Large yeLLow croaker, which were tumor necrosis factorα1(TNF-α1), tumor necrosis factorα2(TNF-α2) and interLeukin 10(IL-10) homoLogue respectiveLy.
In the present study, it was reported that a cLoning from the spLeen cDNA Library from the Large yeLLow croaker is a cystatin homoLogue(Lyccys), with 688 nucLeotides (nt) encoding a protein of 118 amino acids (aa) with a 21aa signaL peptide, 13kDa. The deduced protein shared 27.1-45.9 % , 30.0-31.7 %和16.3-30.6% sequence identity to the sequences found in other fishes, some high vertebrates and some nematodes. The highest sequence identity of 45.9% was achieved by Lyccys and a cystatin from pufferfish. It shared 30.8%, 31.7% sequence identity to the sequences of human cystatin C and chicken egg white cystatin. The Lyccys contains typicaL conserved motifs of cystatin superfamiLy, a N-terminaL GLy-GLy (25, 26), QLVAG (69-73) and a C-terminaL PW (106-107) known to interact with the active site of famiLy Cl cysteine peptidases. There was a conserved S~(52)N~(53) which may be the reactive site of Legumain, a cysteine endopeptidase causing Limited proteoLysis of precursor proteins and protein spLicing. It had the structuraL arrangement of four conserved cysteine residues (C~(56), C~(87), C~(98) and C~(118)) with two disuLphide bonds towards the carboxyL terminusas found in Large known cystatins, however there is a cysteine residue (C~(56)) in the different Location from the others, which was removed to N-terminus. This maybe affected the space structure and its bioLogicaL functions. The genomic DNA sequence of Lyccys was cLoned and sequenced, constituting of three exons and two introns, sharing the simiLar genomic structure with human cystatin C, mouse cystatin C and zebrafish cystatin. Tissue expression profiLe anaLysis with reverse transcription-PCR showed that Lyccys gene was constitutiveLy expressed in aLL eight tissues (intestine, giLL, heart, muscLe, spLeen, Liver, bLood and kidney) examined, aLthough at a different LeveL. The highest LeveL of Lycstefm mRNA was detected in spLeen and kidney, and the Lowest in giLL, muscLe and bLood. The transcript LeveL of Lyccys was increased in kidney and spLeen, but decreased in bLood after induction with poLyI:C or inactivated trivaLent bacteriaL vaccine, anaLysis by reLative quantitative reaL-time PCR. The recombinant Lyccys(GST) (rLyccys(GST)) was expressed in E.coLi BL-21, and purified. The inhibitory specific activity of rLyccys(GST) against papain with the substrate casein was detected to be 40 U/mg. The intraceLLuLar LocaLization of Lyccys in kidney and spLeen ceLLs with immune coLLoidaL goLd eLectron microscopy was suggested that Lyccys was onLy distributed in cytopLasm, mainLy attached to rough endopLasmic reticuLum(rER), Large in vesicLes (endosome or Lysosome), not found in nucLeues. The transcript LeveLs of TNF-α2 and IL-10 were increased in kidney and spLeen of Large yeLLow croaker by injection with rLyccys(GST) through reLative quantitative reaL-time PCR. It is specuLated that the cystatin homoLogue of Large yeLLow croaker probabLy pLay a cardinaL immunomoduLatory roLe simiLar to that of mammaLs.
On the other hand, we reported the cLoning of a stefin gene homoLogue from the spLeen cDNA Library of Large yeLLow croaker (Pseudosciana crocea), an economicaLLy important marine fish (Lycstefm). The fuLL Length cDNA of Lycstefm is 556 nucLeotides (nt) encoding a protein of 99 amino acids (aa0, with a putative moLecuLar weight of 11 kDa. The deduced protein shares 47.5%,47.5%,46.1%, 42.7%,38.0%,38.0% sequence identity to the sequences found in pufferfish, cattLe, takifugu, pig, rainbow trout and zebrafish, respectiveLy; and 43.0%和P 38.0%, 38.4%和 32.0% sequence identity to the sequences of human stefin A, human stefin B, mouse stefin A and mouse stefin B respectiveLy. The deduced Lycstefin contains conserved activation LocaLization of N-terminaL GLy~6-GLy~7 ,a conserved QLVAG (48-51) motif, which were found in aLL stefins. The Lycstefin genomic DNA sequence was cLoned and sequenced, constituting of three exons and two introns, sharing the simiLar genomic structure with human stefin A, mouse stefin A and zebrafish cystatin B. Tissue expression profiLe anaLysis with reverse transcription-PCR (RT-PCR) showed that Lycstefin gene was constitutiveLy expressed in aLL eight tissues (intestine, giLL, heart, muscLe, spLeen, Liver, bLood and kidney) examined, aLthough at a different LeveL. The highest LeveL of Lycstefin mRNA was detected in bLood and kidney, and the Lowest in intestine. The transcript LeveL of Lycstefin was increased in kidney and spLeen , but decreased in bLood after induction with poLyI:C or inactivated trivaLent bacteriaL vaccine, anaLysis by reLative quantitative reaL-time PCR. The recombinant Lycstefin(GST) (rLycstefin(GST)) was expressed in E.coLi BL-21, and purified. The inhibitory specific activity of rLycstefin(GST) against papain with the substrate caseins was detected to be 42 U/mg. The intraceLLuLar LocaLization of Lycstefin in kidney and spLeen with immune coLLoidaL goLd eLectron microscopy was suggested that Lycstefin was mainLy distributed diffuseLy throughout the cytopLasm, and not attached to rough endopLasmic reticuLum(rER) . LittLe was found in nucLeues and vesicLes (endosome or Lysosome). The transcript LeveLs of TNF-α2 and IL-10 were not changed in kidney and spLeen of Large yeLLow croaker by injection with rLyccys(GST) through reLative quantitative reaL-time PCR. So it is suggested that the stefin homoLogue of Large yeLLow croaker couLdn't moduLate The transcript LeveLs of TNF-α2 and IL-10.
引文
[1] 张彩兰，刘有富，李雅璀等．福建省大黄鱼养殖现状分析与对策[J]．上海水产大学学报，2002，11(1)：77-83
[2] Turk, V.: Cysteine Proteinases and Their Inhibitors, Proceedings of the InternationaL Symposium, Portoroz, YugosLavia, (1986) September 15-18. (V. Turk, Ed.) WaLter de Gruyter, BerLin.
[3] Barrett, A. J.: The Cystatins: A New CLass of Peptidase Inhibitors.Trends Biochem. Sci. (1987)12:193-196.
[4] Barrett, A. J. and H. Kirschke: Cathepsin B, Cathepsin H and Cathepsin L. Meth. EnzymoL (1981)80:535-561.
[5] Taugner, R., C. BuhrLe, R. NobiLing, and H. Kirschke: Coexistence of Renin and Cathepsin B in EpitheLioid CeLL Secretory GranuLes. Histochemistry (1985)88:102-108.
[6] Marks, N., M. Berg, and M. Benuck: PreferentiaL, Action of Rat Brain Cathepsin B as a PeptidyL Dipeptidase Converting Pro-Opiod OLigopeptides. Arch. Biochem.Biophys. (1986)249:489-499.
[7] Etherington, D. J. Proteinases in Connective Tissue Breakdown. Protein Degradation in Health and Disease, Ciba Foundation Symposium (1980)VoL. 75, pp. 87-100. (D. Evered and J. WheLan, Eds.) Experta Medica, Amsterdam.
[8] DeLaisse, J.-M., Y. Eeckhoout, and G. Vaes: In Vivo and In Vitro Evidence for the lnvoLvement of Cysteine Proteinases in Bone Resorption. Biochem.Biophys. Res. Commun. (1984)125: 441-447.
[9] SLoane, B. and K. Honn: Cysteine Proteinases and Metastasis. Cancer Metastasis Rev. (1984)3: 249-263.
[10] Barrett, A. J., M. Davies, and A. Grubb: The PLace of Human Gamma-Trace (Cystatin C) Amongst the Cysteine Proteinase Inhibitors. Biochem.Biophys. Res. Commun. (1984)120: 631-636.
[11] Korant, B., T. Towatari, L. Ivanoff, C. Kettner, A. Cordova, and S. Petteway: Viruses as Vectors for Cysteine Proteases. In: Cysteine Proteinases and Their Inhibitors, pp. 293-305. (V. Turk, Ed.) WaLter de Gruyter, BerLin (1986).
[12] Korant, B., T. Towatari, M. KeLLey, J. Brzin, B. Lenarcic, and V. Turk: Interactions between a ViraL Proteinase and Cystatins. BioL. Chem.Hoppe-SeyLer (1988) 369 (SuppL.): 281-286.
[13] Guy B, M. Geist, K. Dott, D. Spehner, M.-P.Kieny, and J.P. Lecocq: A Specific Inhibition of Cysteine Proteinases Impairs a Vif-Dependent Modification of Human Immunodeficiency Virus Type 1 Env Protein. J. ViroL. (1991)65: 1325-1331.
[14] Honey, K. and Rudensky, A.Y. LysosomaL cysteine proteases reguLate antigen presentation. Nat. Rev. ImmunoL. (2003)3, 472-482.
[15] Turk, V., Turk, B. and Turk, D. LysosomaL cysteine proteases: facts and opportunities. EMBO J. (2001)20,4629-4633.
[16] Kos, J. and Lah, T.T. Cysteine proteinases and their endogenous inhibitors: target proteins for prognosis, diagnosis and therapy in cancer (review). OncoL.Rep. (1998)5, 1349-1361.
[17] Lang, A., HorLer, D. and Baici, A. The reLative importance of cysteine peptidases in osteoarthritis. J. RheumatoL. (2000)27, 1970-1979.
[18] Nixon, R.A., CataLdo, A.M. and Mathews, P.M. The endosomaL-LysosomaL system of neurons in ALzheimer's disease pathogenesis: a review. Neurochem.Res. (2000)25,1161-1172.
[19] Lenarcic, B. and Bevec, T. Thyropins - new structuraLLy reLated proteinase inhibitors. BioL.Chem. (1998)379, 105-111.
[20] Liu, N., Raja, S.M., Zazzeroni, F., Metkar, S.S., Shah, R., Zhang, M., Wang, Y., Bromme, D.,Russin, W.A., Lee, J.C., Peter, M.E., FroeLich, C.J., Franzoso, G. and Ashton-Rickardt, P.G.NF-kappaB protects from the LysosomaL pathway of ceLL death. EMBO J. (2003)22,5313-5322.
[21] Turk, B., Turk, V. and Turk, D. StructuraL and functionaL aspects of papain-Like cysteine proteinases and their protein inhibitors. BioL. Chem. (1997)378, 141-150.
[22]Libuse A Bobek and MichaeL J Levine. Cystatins—inhibitors of cysteine proteinases, CriticaL Reviews in OraL BioLogy and Medicine, (1992)3(4):307-332.
[23] Fossum, K. and J. R. Whitaker: Ficin and Papain Inhibitor from Chicken Egg White. Arch.Biochem. Biophys. (1968)125: 367-375.
[24] Sen, L. C. and J. R. Whitaker: Some Properties of a Ficin- Papain Inhibitor from Avian Egg White. Arch. Biochem.Biophys. (1973)158: 623-632.
[25] KeiLova, H. and V. Tomasek: Effect of Papain Inhibitor from Chicken Egg White on Cathepsin B,.Biochem.Biophys. Ada (1974)334: 179-186.
[26] Barrett, A. J. and H. Kirschke: Cathepsin B, Cathepsin H and Cathepsin L. Meth. EnzymoL (1981)80:535-561.
[27] Anastasi, A., M. A. Brown, A. A. Kembhavi, M. J. H. NickLin, C. A. Sayers, D. C. Sunter, and A. J. Barrett: Cystatin, a Protein Inhibitor of Cysteine Proteinases. Biochem J. (1983)211:129-138.
[28] Turk, V., J. Brzin, B. Lenarcic, P. Locnikar, T. Popovic, A. Ritonja, J. Babnik, W. Bode, and W. MachLeidt: Structure and Function of LysosomaL Cysteine Proteinases and Their Protein Inhibitors. In: MraceLLuLar Protein CataboLism, (1985)91-103.
[29] Barrett, A. J., H. Fritz, A. Grubb, S. Isemura, M. Jarvinen, N. Katunuma, W. MachLeidt, W.MuLLer-EsterL, M. Sasaki, and V. Turk: NomencLature and Classification of the Proteins HomoLogous with the Cysteine-Proteinase Inhibitor Chicken Cystatin. Biochem.J.(1986b)236:312.
[30] Abe, K., Y. Emori, H. Kondo, S. Arai, and K. Suzuki: The NH2-TerminaL 21 Amino Acid Residues Are Not EssentiaL for the Papain-Inhibitory Activity of Oryzacystatin, a Member of the Cystatin SuperfamiLy. J. BioL.Chem. (1988)263: 7655-7659.
[31] Brzin, J., A. Ritonja, T. Popovic, and V. Turk: Low MoLecuLar Mass Protein Inhibitor of Cysteine Proteinases from Soybean. BioL. Chem. Hoppe-SeyLer (1990)371 (SuppL.):167-170.
[32] RawLings, N.D., ToLLe, D.P. and Barrett, A.J. EvoLutionary famiLies of peptidase inhibitors.BiochemJ. (2004)378, 705-716.
[33] RawLings, N.D., Morton, F.R. and Barrett, A.J. MEROPS: the peptidase database. NucLeic Acids Res. (2006)34, D270-D272.
[34] Bode, W., R. Engh, D. MusiL, U. ThieLe, R. Huber, A. Karshikov, J. Brzin, J. Kos, and V.Turk: The 2.0 A X-Ray CrystaL Structure of Chicken Egg White Cystatin and Its PossibLe Mode of Interaction with Cysteine Proteinases. EMBO J. (1988)7:2593-2599.
[35] Bode, W., R. Engh, D. MusiL, B. Laber, M. Stubbs, R. Huber, and V. Turk: Mechanism of Interaction of Cysteine Proteinases and Their Protein Inhibitors as Compared to the Serine Proteinase-lnhibitor Interaction. BioL.Chem.Hoppe-SeyLer (1990)371:111-118.
[36] MachLeidt, W., U. ThieLe, B. Laber, I. AssfaLg-MachLeidt, A. EsterL, G. Wiegand, J. Kos, V. Turk, and W. Bode: Mechanism of Inhibition of Papain by Chicken Egg White Cystatin. FEBS Lett. (1989)243:234-238.
[37] Stubbs MT, Laber B, and et aL. The refined 2.4 A X-ray crystaL structure of recombinant human stefin B in compLex with the cysteine proteinase papain: a noveL type of proteinase inhibitor interaction. EMBO J. (1990) 9(6): 1939-47.
[38] Luminita Paraoan, Ian Grierson. Focus on MoLecuLes: Cystatin C. ExperimentaL Eye Research (2007)84, 1019-1020
[39] Paraoan, L., White, M.R.H., SpiLLer, D.G., Grierson, I.,Maden, B.E.H., Precursor cystatin C in cuLtured retinaL pigment epitheLium ceLLs: evidence for processing through the secretory pathway. MoL. Membr. BioL. (2001)18, 229-236.
[40] ZurdeL, J., Finckh, U., Menzer, G., Nitsch, R.M., Richard, G., CST3 genotype associated with exudative age reLated macuLar degeneration. Br. J. OphthaLmoL. (2002)86, 214-219.
[40] Brzin, J., Kopitar, M., Locnikar, P. and Turk, V. An endogenous inhibitor of cysteine and serine proteinases from spLeen. FEBS Lett. (1982)138, 193-197.
[41] Brzin, J., Kopitar, M., Turk, V. and MachLeidt, W. Protein inhibitors of cysteine proteinases. 1.IsoLation and characterization of stefin, a cytosoLic protein inhibitor of cysteine proteinases from human poLymorphonucLear granuLocytes. Hoppe SeyLers Z. PhysioL Chem. (1983)364,1475-1480.
[42] Green, G.D., Kembhavi, A.A., Davies, M.E. and Barrett, A.J. Cystatin-Like cysteine proteinase inhibitors from human Liver. Biochem. J. (1984)218, 939-946.
[43] Jarvinen, M. Purification and some characteristics of the human epidermaL SH-protease inhibitor. J. Invest DermatoL. (1978)71, 114-118.
[44] Suzuki, T., Hashimoto, S., Toyoda, N., Nagai, S., Yamazaki, N., Dong, H.Y., Sakai, J.,Yamashita, T., Nukiwa, T. and Matsushima, K. Comprehensive gene expression profiLe of LPSstimuLated human monocytes by SAGE. BLood (2000)96, 2584-2591.
[45] Rinne, A., Dorn, A., Jarvinen, M., ALavaikko, M., Jokinen, K. and Hopsu-Havu, V.K.ImmunoeLectron microscopicaL Location of the acid cysteine proteinase inhibitor in the Lymphatic tissue of the tonsiLs. Acta Histochem. (1986)79, 137-145.
[46] Burton, G.F., Conrad, D.H., SzakaL, A.K. and Tew, J.G. FoLLicuLar dendritic ceLLs and B ceLL costimuLation. J. ImmunoL. (1993)150, 31-38.
[47] Fu, Y.X. and ChapLin, D.D. DeveLopment and maturation of secondary Lymphoid tissues.Annu. Rev. ImmunoL. (1999)17, 399-433.
[48] Park, C.S. and Choi, Y.S. How do foLLicuLar dendritic ceLLs interact intimateLy with B ceLLs in the germinaL centre. ImmunoLogy (2005)114,2-10.
[49] Tew, J.G., Wu, J., Qin, D., HeLm, S., Burton, G.F. and SzakaL, A.K. FoLLicuLar dendritic ceLLs and presentation of antigen and costimuLatory signaLs to B ceLLs. ImmunoL. Rev.(1997)156,39-52.
[50] Liu, Y.J., Joshua, D.E., WiLLiams, G.T., Smith, C.A., Gordon, J. and MacLennan, I.C. Mechanism of antigen-driven seLection in germinaL centres. Nature (1989)342,929-931.
[51] Liu, Y.J., Arpin, C., de BouteiLLer, O., Guret, C., Banchereau, J., Martinez-VaLdez, H. and Lebecque, S. SequentiaL triggering of apoptosis, somatic mutation and isotype switch during germinaL center deveLopment. Semin. ImmunoL. (1996)8, 169-177.
[52] MacLennan, J.C. GerminaL centers. Annu. Rev. ImmunoL. (1994)12,117-139.
[53] Hennino, A., Berard, M., Krammer, P.H. and Defrance, T. FLICE-inhibitory protein is a key reguLator of germinaL center B ceLL apoptosis. J. Exp. Med. 193(2001), 447-458.
[54] van Eijk, M., Medema, J.P. and de Groot, C. Cutting edge: ceLLuLar Fas-associated death domain-Like IL-1-converting enzyme-inhibitory protein protects germinaL center B ceLLs from apoptosis during germinaL center reactions. J. ImmunoL. (2001)166, 6473-6476.
[55] van Eijk, M., Defrance, T., Hennino, A. and de Groot, C. Death-receptor contribution to the germinaL-center reaction. Trends ImmunoL. (2001)22, 677-682.
[56] Lindhout, E., Lakeman, A. and de Groot, C. FoLLicuLar dendritic ceLLs inhibit apoptosis in human B Lymphocytes by a rapid and irreversibLe bLockade of preexisting endonucLease. J.Exp. Med. (1995)181, 1985-1995.
[57] van Eijk, M. and de Groot, C. GerminaL center B ceLL apoptosis requires both caspase and cathepsin activity. J. ImmunoL. (1999)163, 2478-2482.
[58] van Nierop, K., MuLLer, F.J., Stap, J., Van Noorden, C.J., van Eijk, M., and de Groot, C.LysosomaL destabiLization contributes to apoptosis of germinaL center B-Lymphocytes. J.Histochem. Cytochem. (2006) VoLume 54 (12): 1425-1435.
[59] van Eijk, M., Van Noorden, C.J. and de Groot, C. Proteinases and their inhibitors in the immune system. Int. Rev. CytoL. (2003)222, 197-236.
[60] LindahL, P., Abrahamson, M. and Bjork, 1. Interaction of recombinant human cystatin C with the cysteine proteinases papain and actinidin. Biochem. J. (1992)281,49-55.
[61] Abrahamson, M., Barrett, A.J., SaLvesen, G. and Grubb, A. IsoLation of six cysteine proteinase inhibitors from human urine. Their physicochemicaL and enzyme kinetic properties and concentrations in bioLogicaL fLuids. J. BioL. Chem. (1986)261,11282- 11289.
[62] Abrahamson, M., OLafsson, I., PaLsdottir, A., ULvsback, M., LundwaLL, A., Jensson, O. and Grubb, A. Structure and expression of the human cystatin C gene. Biochem. J. (1990)268,287-294.
[63] Abrahamson, M., Jonsdottir, S., OLafsson, I., Jensson, O. and Grubb, A. Hereditary cystatin C amyLoid angiopathy: identification of the disease-causing mutation and specific diagnosis by poLymerase chain reaction based anaLysis. Hum. Genet. (1992)89, 377-380.
[64] Merz, G.S., Benedikz, E., Schwenk, V., Johansen, T.E., VogeL, L.K., Rushbrook, J.L. and Wisniewski, H.M. Human cystatin C forms an inactive dimer during intraceLLuLar trafficking in transfected CHO ceLLs. J. CeLL PhysioL. (1997)173, 423-432.
[65] Huh, C.G., Hakansson, K., Nathanson, C.M., Thorgeirsson, U.P., Jonsson, N., Grubb, A.,Abrahamson, M. and KarLsson, S. Decreased metastatic spread in mice homozygous for a nuLL aLLeLe of the cystatin C protease inhibitor gene. MoL. PathoL. (1999)52, 332-340.
[66] Bengtsson, E., To, F., Hakansson, K., Grubb, A., Branen, L., NiLsson, I. and Jovinge, S. Lack of the cysteine protease inhibitor cystatin C promotes atheroscLerosis in apoLipoprotein E-deficient mice. ArterioscLer. Thromb. Vase. BioL. (2005)25, 2151-2156.
[67] Taupin, P., Ray, J., Fischer, W.H., Suhr, S.T., Hakansson, K., Grubb, A. and Gage, F.H. FGF-2-responsive neuraL stem ceLL proLiferation requires CCg, a noveL autocrine/paracrine cofactor. Neuron (2000)28, 385-397.
[68] MeLLman, I. and Steinman, R.M. Dendritic ceLLs: speciaLized and reguLated antigen processing machines. CeLL (2001)106,255-258.
[69] Hunt, D.F., MicheL, H., Dickinson, T.A., Shabanowitz, J., Cox, A.L., Sakaguchi, K., AppeLLa,E., Grey, H.M. and Sette, A. Peptides presented to the immune system by the murine cLass Ⅱ major histocompatibiLity compLex moLecuLe I-Ad. Science (1992)256, 1817-1820.
[70] Hashimoto, S., Suzuki, T., Dong, H.Y., Nagai, S., Yamazaki, N. and Matsushima, K. SeriaL anaLysis of gene expression in human monocyte-derived dendritic ceLLs. BLood (1999)94, 845-852.
[71] Zavasnik-Bergant, T., Repnik, U., Schweiger, A., Romih, R., Jeras, M., Turk, V. and Kos, J.Differentiation- and maturation-dependent content, LocaLization, and secretion of cystatin C in human dendritic ceLLs. J. Leukoc. BioL. (2005)78, 122-134.
[72] Pierre, P. and MeLLman, I. DeveLopmentaL reguLation of invariant chain proteoLysis controLs MHC cLass Ⅱ trafficking in mouse dendritic ceLLs. CeLL (1998)93, 1135-1145.
[73] EL Sukkari, D., WiLson, N.S., Hakansson, K., Steptoe, R.J., Grubb, A., Shortman,K. and ViLLadangos, J.A. The protease inhibitor cystatin C is differentiaLLy expressed among dendritic ceLL popuLations, but does not controL antigen presentation. J. ImmunoL. (2003)171,5003-5011.
[74] Kitamura, H., Kamon, H., Sawa, S., Park, S.J., Katunuma, N., Ishihara, K., Murakami, M. and Hirano, T. IL-6-STAT3 controLs intraceLLuLar MHC cLass Ⅱ aLphabeta dimer LeveL through cathepsin S activity in dendritic ceLLs. Immunity (2005)23,491-502.
[75] Edwards, A.D., ChaussabeL, D., TomLinson, S., SchuLz, O., Sher, A. and Reise Sousa, C.ReLationships among murine CD11c(high) dendritic ceLL subsets as reveaLed by baseLine gene expression patterns. J. ImmunoL. (2003)171, 47-60.
[76] Vremec, D., PooLey, J., Hochrein, H., Wu, L. and Shortman, K. CD4 and CDS expression by dendritic ceLL subtypes in mouse thymus and spLeen. J. ImmunoL. (2000)164, 2978-2986.
[77] PuLendran, B., Smith, J.L., Caspary, G., BraseL, K., Pettit, D., Maraskovsky, E. and MaLiszewski, C.R. Distinct dendritic ceLL subsets differentiaLLy reguLate the cLass of immune response in vivo. Proc. NatL Acad. Sci. USA (1999)96, 1036-1041.
[78] MaLdonado-Lopez, R., De Smedt, T., MicheL, P., Godfroid, J., Pajak, B., Heirman, C.ThieLemans, K., Leo, O., Urbain, J. and Moser, M. CD8aLpha+ and CD8aLpha-subcLasses of dendritic ceLLs direct the deveLopment of distinct T heLper ceLLs in vivo. J. Exp. Med.(1999)189,587-592.
[79] Hochrein, H., Shortman, K., Vremec, D., Scott, B., Hertzog, P. and O'Keeffe, M. DifferentiaL production of IL-12, IFNaLpha, and IFN-gamma by mouse dendritic ceLL subsets. J. ImmunoL.(2001)166,5448-5455.
[80] den Haan, J.M., Lehar, S.M. and Bevan, M.J. CD8(+) but not CD8(_) dendritic ceLLs cross-prime cytotoxic T ceLLs in vivo. J. Exp. Med. (2000)192, 1685-1696.
[81] den Haan, J.M. and Bevan, M.J. Antigen presentation to CD8+T ceLLs: cross-priming in infectious diseases. Curr. Opin. ImmunoL. (2001)13, 437-441.
[82] Heath, W.R., BeLz, G.T., Behrens, G.M, Smith, C.M., Forehan, S.P., Parish, J.A., Davey, G.M., WiLson, N.S., Carbone, F.R. and ViLLadangos, J.A. Cross-presentation, dendritic ceLL subsets, and the generation of immunity to ceLLuLar antigens. ImmunoL. Rev. (2004)199, 9-26.
[83] BeLz, G.T., Shortman, K., Bevan, M.J. and Heath, W.R. CD8aLpha+ dendritic ceLLs seLectiveLy present MHC cLass Irestricted noncytoLytic viraL and intraceLLuLar bacteriaL antigens in vivo. J. ImmunoL. (2005)175, 196-200.
[84] LaLioti, M.D., Mirotsou, M., Buresi, C., Peitsch, M.C., Rossier, C., Ouazzani, R., BaLdy-MouLinier, M., Bottani, A., MaLafosse, A. and Antonarakis, S.E. Identification of mutations in cystatin B, the gene responsibLe for the Unverricht-Lundborg type of progressive myocLonus epiLepsy (EPM1). Am. J. Hum. Genet. (1997)60, 342-351.
[85] LaLioti, M.D., Scott, H.S., Buresi, C., Rossier, C., Bottani, A., Morris, M.A., MaLafosse, A. and Antonarakis, S.E. Dodecamer repeat expansion in cystatin B gene in progressive myocLonus epiLepsy. Nature (1997)386, 847-851.
[86] Pennacchio, L.A., Lehesjoki, A.E., Stone, N.E., WiLLour, V.L., Virtaneva, K., Miao, J.,D'Amato, E., Ramirez, L., Faham, M., Koskiniemi, M., Warrington, J.A., Norio, R., de La ChapeLLe, A., Cox, D.R. and Myers, R.M. Mutations in the gene encoding cystatin B in progressive myocLonus epiLepsy (EPM1). Science (1996)271, 1731-1734.
[87] Pennacchio, L.A., BouLey, D.M., Higgins, K.M., Scott, M.P., NoebeLs, J.L. and Myers, R.M. Progressive ataxia, myocLonic epiLepsy and cerebeLLar apoptosis in cystatin B-deficient mice.Nat. Genet. (1998)20, 251-258.
[88] LieuaLLen, K., Pennacchio, L.A., Park, M., Myers, R.M. and Lennon, G.G. Cystatin B-deficient mice have increased expression of apoptosis and gLiaL activation genes. Hum. Mot Genet.(2001)10, 1867-1871.
[89] Houseweart, M.K., Pennacchio, L.A., ViLaythong, A., Peters, C., NoebeLs, J.L. and Myers,R.M. Cathepsin B but not cathepsins L or S contributes to the pathogenesis of Unverricht-Lundborg progressive myocLonus epiLepsy (EPM1). J. NeurobioL. (2003)56,315-327.
[90] Kopitar-JeraLa, N., Schweiger, A., Myers, R.M., Turk, V. and Turk, B. Sensitization of stefin B-deficient thymocytes towards staurosporin-induced apoptosis is independent of cysteine cathepsins. FEBS Lett. (2005)579, 2149-2155.
[91] BrannvaLL, K., HjeLm, H., Korhonen, L., Lahtinen, U., Lehesjoki, A.E. and LindhoLm, D. Cystatin-B is expressed by neuraL stem ceLLs and by differentiated neurons and astrocytes. Biochem. Biophys. Res. Commun. (2003)308, 369-374.
[92] Hashimoto, S., Suzuki, T., Dong, H.Y., Yamazaki, N. and Matsushima, K. SeriaL anaLysis of gene expression in human monocytes and macrophages. BLood (1999)94, 837-844.
[93] Verdot, L., LaLmanach, G., Vercruysse, V., Hartmann, S., Lucius, R., Hoebeke, J., Gauthier, F.and Vray, B. Cystatins upreguLate nitric oxide reLease from interferon-gamma-activated mouse peritoneaL macrophages. J. BioL. Chem. (1996)271, 28077-28081.
[94] Verdot, L., LaLmanach, G., Vercruysse, V., Hoebeke, J., Gauthier, F. and Vray, B. Chicken cystatin stimuLates nitric oxide reLease from interferon-gamma-activated mouse peritoneaL macrophages via cytokine synthesis. Eur. J. Biochem. (1999)266, 1111-1117.
[95] Das, L., Datta, J.N.L., Bandyopadhyay, S. and Das, P.K. SuccessfuL therapy of LethaL murine visceraL Leishmaniasis with cystatin invoLves up-reguLation of nitric oxide and a favorabLe T ceLL response. J. immunoL. (2001)166, 4020-4028.
[96] Natasa Kopitar-JeraLa. The roLe of cystatins in ceLLs of the immune system. FEBS Letters.(2006)580,6295-6301.
[97] Hartmann, S., B. Kyewski, B. Sonnenburg, and R. Lucius. A fiLariaL cysteine protease inhibitor down-reguLates T-ceLL proLiferation and enhances interLeukin-10 production. Eur. J. ImmunoL. (1997)27: 2253-2260.
[98] Scho nemeyer, A., R. Lucius, B. Sonnenburg, N. Brattig, R. Sabat, K. SchiLLing, J. BradLey,and S. Hartmann. ModuLation of human T-ceLL responses and macrophage functions by onchocystatin, a secreted protein of the fiLariaL nematode Onchocerca voLvuLus. J. ImmunoL.(2001)167:3207-3215.
[99] Manoury, B., W. F. Gregory, R. M. MaizeLs, and C. Watts. Bm-CPI-2, a cystatin homoLog secreted by the fiLariaL parasite Brugia maLayi, inhibits cLass II MHC-restricted antigen processing. Curr. BioL. (2001)11: 447-451.
[100]Pfaff, A. W., H. SchuLz-Key, P. T. SobosLay, D. W. TayLor, K. MacLennan, and W. H. Hoffmann. Litomosoides sigmodontis cystatin acts as an immunomoduLator during experimental. fiLariasis. Int. J. ParasitoL. (2002)32: 171-178.
[101] Maekawa, Y., K. Himeno, H. Ishikawa, H. Hisaeda, T. Sakai, T. Dainichi, T. Asao, R. A. Good, and N. Katunuma. Switch of CD4_ T-ceLL differentiation from Th2 to Th1 by treatment with cathepsin B inhibitor in experimentaL Leishmaniasis. J. ImmunoL. (1998)161:2120-2127.
[102]Mosmann, T. R. Properties and functions of interLeukin-10. Adv. ImmunoL. (1994)56:1-26.
[103]Korant, B., J. Brzin, and V. Turk. Cystatin, a protein inhibitor of cysteine proteinases aLters viraL protein cLeavages in infected human ceLLs. Biochem. Biophys. Res. Commun. (1985)127: 1072-1076.
[104] Fugen Li, Haejung An, Thomas A. Seymour, David W. Barnes. Rainbow trout (Oncorhynchus mykiss) cystatin C: expression in Escherichia coLi and properties of the recombinant protease inhibitor. Comparative Biochemistry and PhysioLogy Part B (2000)125: 493-502.
[105] Li, F., An, H., Seymour, T.A., Bradford, C.S., Morrissey, M.T., BaiLey, G.S., Barnes, D.W.,MoLecuLar cLoning, sequence anaLysis and expression distribution of rainbow trout (Oncorhynchus mykiss) cystatin C. J. Comp. Biochem. PhysioL. B (1998)121, 135-143.
[106] J(a|¨)rvinen M, Rinne A. Human spLeen cyteine proteinase inhibitor. Purification,fractionation into isoeLectric variants and some properties of the variants. Biochim Biophys Acta.(1982)708:210-217.
[107] Green GDJ, Kembhavi AA, Davies ME, Barrett AJ. CystatinLike cysteine proteinase inhibitors from human Liver. Biochem J.(1984)218:939-946.
[108] Abrahamson M, Barrett AJ, SaLvesen G, Grubb A. IsoLation of six cysteine proteinase inhibitors from human urine. J BioL Chem(1986)261:11282-11289.
[109] SLoane BF, Moin K, Sameni M, Tait LR, Rozhin J, ZiegLer G. Membrane association of cathepsin B can be induced by transfection of human breast epitheLiaL ceLLs with c-Haras oncogene. J CeLL Sci. (1994b) 107: 373-384.
[110] Sameni M, ELLiott E, ZiegLer G, Fortgens PH, Dennison C, SLoane BF. Cathepsins B and D are LocaLized at surface of human breast cancer ceLLs. PathoL OncoL Res (1995)1:43—53.
[111] Catharine C. CaLkins, Mansoureh Sameni, Jennifer KobLinski, Bonnie F. SLoane, and Kamiar Moin. DifferentiaL LocaLization of Cysteine Protease Inhibitors and a Target Cysteine Protease, Cathepsin B, by Immuno-ConfocaL Microscopy. The JournaL of Histochemistry & Cytochemistry,(1998) VoLume 46(6): 745-751,
[112]GosseLin EJ, Cate CC, PettengiLL OS, et aL. Immunocutochemistry: Its evoLution and criteria for its appLication in the study of epon-embedded ceLLs and tissues. Am J Anat, (1986)175:135-160.
[113]Toru Hosoi, Sawako Suzuki, and et aL. LPS induces stefin A3 expression in mouse primary cuLtured gLiaL ceLLs. MoLecuLar Brain Research (2005)140: 138-141.
[114] BeutLer, B.A. & Van HuffeL, C. (1994) UnraveLing function in the TNF Ligand and receptor famiLies. Science 264, 667?68.
[115] Howard, M., O'Garra, A., Ishida, H., de WaaL MaLefyt, R. & de Vries, J. (1992) BioLogicaL properties of interLeukin 10. J. CLin. ImmunoL. 12, 239±247.
[116] Peter Schierack, Richard Lucius, and et aL. Parasite-Specific ImmunomoduLatory Functions of FiLariaL Cystatin. Infection and Immunity, (2003) VoL. 71, No. 5,2422-2429.
[117] Marcia ALvarez-Fernandez, ALan J. Barrett and et aL. Inhibition of MammaLian Legumain by Some Cystatins Is Due to a NoveL Second Reactive Site, the JournaL of BioLogicaL Chemistry. (1999) VoL. 274, No. 27, Issue of JuLy 2, pp. 19195-19203.
[118] 马冬梅 一， 白俊杰， 劳海华等。中华鲟半胱氨酸蛋白酶抑制剂C基因的原核表达。(2003)VoL．27，No．3，239-244。
[2] Turk, V.: Cysteine Proteinases and Their Inhibitors, Proceedings of the InternationaL Symposium, Portoroz, YugosLavia, (1986) September 15-18. (V. Turk, Ed.) WaLter de Gruyter, BerLin.
[3] Barrett, A. J.: The Cystatins: A New CLass of Peptidase Inhibitors.Trends Biochem. Sci. (1987)12:193-196.
[4] Barrett, A. J. and H. Kirschke: Cathepsin B, Cathepsin H and Cathepsin L. Meth. EnzymoL (1981)80:535-561.
[5] Taugner, R., C. BuhrLe, R. NobiLing, and H. Kirschke: Coexistence of Renin and Cathepsin B in EpitheLioid CeLL Secretory GranuLes. Histochemistry (1985)88:102-108.
[6] Marks, N., M. Berg, and M. Benuck: PreferentiaL, Action of Rat Brain Cathepsin B as a PeptidyL Dipeptidase Converting Pro-Opiod OLigopeptides. Arch. Biochem.Biophys. (1986)249:489-499.
[7] Etherington, D. J. Proteinases in Connective Tissue Breakdown. Protein Degradation in Health and Disease, Ciba Foundation Symposium (1980)VoL. 75, pp. 87-100. (D. Evered and J. WheLan, Eds.) Experta Medica, Amsterdam.
[8] DeLaisse, J.-M., Y. Eeckhoout, and G. Vaes: In Vivo and In Vitro Evidence for the lnvoLvement of Cysteine Proteinases in Bone Resorption. Biochem.Biophys. Res. Commun. (1984)125: 441-447.
[9] SLoane, B. and K. Honn: Cysteine Proteinases and Metastasis. Cancer Metastasis Rev. (1984)3: 249-263.
[10] Barrett, A. J., M. Davies, and A. Grubb: The PLace of Human Gamma-Trace (Cystatin C) Amongst the Cysteine Proteinase Inhibitors. Biochem.Biophys. Res. Commun. (1984)120: 631-636.
[11] Korant, B., T. Towatari, L. Ivanoff, C. Kettner, A. Cordova, and S. Petteway: Viruses as Vectors for Cysteine Proteases. In: Cysteine Proteinases and Their Inhibitors, pp. 293-305. (V. Turk, Ed.) WaLter de Gruyter, BerLin (1986).
[12] Korant, B., T. Towatari, M. KeLLey, J. Brzin, B. Lenarcic, and V. Turk: Interactions between a ViraL Proteinase and Cystatins. BioL. Chem.Hoppe-SeyLer (1988) 369 (SuppL.): 281-286.
[13] Guy B, M. Geist, K. Dott, D. Spehner, M.-P.Kieny, and J.P. Lecocq: A Specific Inhibition of Cysteine Proteinases Impairs a Vif-Dependent Modification of Human Immunodeficiency Virus Type 1 Env Protein. J. ViroL. (1991)65: 1325-1331.
[14] Honey, K. and Rudensky, A.Y. LysosomaL cysteine proteases reguLate antigen presentation. Nat. Rev. ImmunoL. (2003)3, 472-482.
[15] Turk, V., Turk, B. and Turk, D. LysosomaL cysteine proteases: facts and opportunities. EMBO J. (2001)20,4629-4633.
[16] Kos, J. and Lah, T.T. Cysteine proteinases and their endogenous inhibitors: target proteins for prognosis, diagnosis and therapy in cancer (review). OncoL.Rep. (1998)5, 1349-1361.
[17] Lang, A., HorLer, D. and Baici, A. The reLative importance of cysteine peptidases in osteoarthritis. J. RheumatoL. (2000)27, 1970-1979.
[18] Nixon, R.A., CataLdo, A.M. and Mathews, P.M. The endosomaL-LysosomaL system of neurons in ALzheimer's disease pathogenesis: a review. Neurochem.Res. (2000)25,1161-1172.
[19] Lenarcic, B. and Bevec, T. Thyropins - new structuraLLy reLated proteinase inhibitors. BioL.Chem. (1998)379, 105-111.
[20] Liu, N., Raja, S.M., Zazzeroni, F., Metkar, S.S., Shah, R., Zhang, M., Wang, Y., Bromme, D.,Russin, W.A., Lee, J.C., Peter, M.E., FroeLich, C.J., Franzoso, G. and Ashton-Rickardt, P.G.NF-kappaB protects from the LysosomaL pathway of ceLL death. EMBO J. (2003)22,5313-5322.
[21] Turk, B., Turk, V. and Turk, D. StructuraL and functionaL aspects of papain-Like cysteine proteinases and their protein inhibitors. BioL. Chem. (1997)378, 141-150.
[22]Libuse A Bobek and MichaeL J Levine. Cystatins—inhibitors of cysteine proteinases, CriticaL Reviews in OraL BioLogy and Medicine, (1992)3(4):307-332.
[23] Fossum, K. and J. R. Whitaker: Ficin and Papain Inhibitor from Chicken Egg White. Arch.Biochem. Biophys. (1968)125: 367-375.
[24] Sen, L. C. and J. R. Whitaker: Some Properties of a Ficin- Papain Inhibitor from Avian Egg White. Arch. Biochem.Biophys. (1973)158: 623-632.
[25] KeiLova, H. and V. Tomasek: Effect of Papain Inhibitor from Chicken Egg White on Cathepsin B,.Biochem.Biophys. Ada (1974)334: 179-186.
[26] Barrett, A. J. and H. Kirschke: Cathepsin B, Cathepsin H and Cathepsin L. Meth. EnzymoL (1981)80:535-561.
[27] Anastasi, A., M. A. Brown, A. A. Kembhavi, M. J. H. NickLin, C. A. Sayers, D. C. Sunter, and A. J. Barrett: Cystatin, a Protein Inhibitor of Cysteine Proteinases. Biochem J. (1983)211:129-138.
[28] Turk, V., J. Brzin, B. Lenarcic, P. Locnikar, T. Popovic, A. Ritonja, J. Babnik, W. Bode, and W. MachLeidt: Structure and Function of LysosomaL Cysteine Proteinases and Their Protein Inhibitors. In: MraceLLuLar Protein CataboLism, (1985)91-103.
[29] Barrett, A. J., H. Fritz, A. Grubb, S. Isemura, M. Jarvinen, N. Katunuma, W. MachLeidt, W.MuLLer-EsterL, M. Sasaki, and V. Turk: NomencLature and Classification of the Proteins HomoLogous with the Cysteine-Proteinase Inhibitor Chicken Cystatin. Biochem.J.(1986b)236:312.
[30] Abe, K., Y. Emori, H. Kondo, S. Arai, and K. Suzuki: The NH2-TerminaL 21 Amino Acid Residues Are Not EssentiaL for the Papain-Inhibitory Activity of Oryzacystatin, a Member of the Cystatin SuperfamiLy. J. BioL.Chem. (1988)263: 7655-7659.
[31] Brzin, J., A. Ritonja, T. Popovic, and V. Turk: Low MoLecuLar Mass Protein Inhibitor of Cysteine Proteinases from Soybean. BioL. Chem. Hoppe-SeyLer (1990)371 (SuppL.):167-170.
[32] RawLings, N.D., ToLLe, D.P. and Barrett, A.J. EvoLutionary famiLies of peptidase inhibitors.BiochemJ. (2004)378, 705-716.
[33] RawLings, N.D., Morton, F.R. and Barrett, A.J. MEROPS: the peptidase database. NucLeic Acids Res. (2006)34, D270-D272.
[34] Bode, W., R. Engh, D. MusiL, U. ThieLe, R. Huber, A. Karshikov, J. Brzin, J. Kos, and V.Turk: The 2.0 A X-Ray CrystaL Structure of Chicken Egg White Cystatin and Its PossibLe Mode of Interaction with Cysteine Proteinases. EMBO J. (1988)7:2593-2599.
[35] Bode, W., R. Engh, D. MusiL, B. Laber, M. Stubbs, R. Huber, and V. Turk: Mechanism of Interaction of Cysteine Proteinases and Their Protein Inhibitors as Compared to the Serine Proteinase-lnhibitor Interaction. BioL.Chem.Hoppe-SeyLer (1990)371:111-118.
[36] MachLeidt, W., U. ThieLe, B. Laber, I. AssfaLg-MachLeidt, A. EsterL, G. Wiegand, J. Kos, V. Turk, and W. Bode: Mechanism of Inhibition of Papain by Chicken Egg White Cystatin. FEBS Lett. (1989)243:234-238.
[37] Stubbs MT, Laber B, and et aL. The refined 2.4 A X-ray crystaL structure of recombinant human stefin B in compLex with the cysteine proteinase papain: a noveL type of proteinase inhibitor interaction. EMBO J. (1990) 9(6): 1939-47.
[38] Luminita Paraoan, Ian Grierson. Focus on MoLecuLes: Cystatin C. ExperimentaL Eye Research (2007)84, 1019-1020
[39] Paraoan, L., White, M.R.H., SpiLLer, D.G., Grierson, I.,Maden, B.E.H., Precursor cystatin C in cuLtured retinaL pigment epitheLium ceLLs: evidence for processing through the secretory pathway. MoL. Membr. BioL. (2001)18, 229-236.
[40] ZurdeL, J., Finckh, U., Menzer, G., Nitsch, R.M., Richard, G., CST3 genotype associated with exudative age reLated macuLar degeneration. Br. J. OphthaLmoL. (2002)86, 214-219.
[40] Brzin, J., Kopitar, M., Locnikar, P. and Turk, V. An endogenous inhibitor of cysteine and serine proteinases from spLeen. FEBS Lett. (1982)138, 193-197.
[41] Brzin, J., Kopitar, M., Turk, V. and MachLeidt, W. Protein inhibitors of cysteine proteinases. 1.IsoLation and characterization of stefin, a cytosoLic protein inhibitor of cysteine proteinases from human poLymorphonucLear granuLocytes. Hoppe SeyLers Z. PhysioL Chem. (1983)364,1475-1480.
[42] Green, G.D., Kembhavi, A.A., Davies, M.E. and Barrett, A.J. Cystatin-Like cysteine proteinase inhibitors from human Liver. Biochem. J. (1984)218, 939-946.
[43] Jarvinen, M. Purification and some characteristics of the human epidermaL SH-protease inhibitor. J. Invest DermatoL. (1978)71, 114-118.
[44] Suzuki, T., Hashimoto, S., Toyoda, N., Nagai, S., Yamazaki, N., Dong, H.Y., Sakai, J.,Yamashita, T., Nukiwa, T. and Matsushima, K. Comprehensive gene expression profiLe of LPSstimuLated human monocytes by SAGE. BLood (2000)96, 2584-2591.
[45] Rinne, A., Dorn, A., Jarvinen, M., ALavaikko, M., Jokinen, K. and Hopsu-Havu, V.K.ImmunoeLectron microscopicaL Location of the acid cysteine proteinase inhibitor in the Lymphatic tissue of the tonsiLs. Acta Histochem. (1986)79, 137-145.
[46] Burton, G.F., Conrad, D.H., SzakaL, A.K. and Tew, J.G. FoLLicuLar dendritic ceLLs and B ceLL costimuLation. J. ImmunoL. (1993)150, 31-38.
[47] Fu, Y.X. and ChapLin, D.D. DeveLopment and maturation of secondary Lymphoid tissues.Annu. Rev. ImmunoL. (1999)17, 399-433.
[48] Park, C.S. and Choi, Y.S. How do foLLicuLar dendritic ceLLs interact intimateLy with B ceLLs in the germinaL centre. ImmunoLogy (2005)114,2-10.
[49] Tew, J.G., Wu, J., Qin, D., HeLm, S., Burton, G.F. and SzakaL, A.K. FoLLicuLar dendritic ceLLs and presentation of antigen and costimuLatory signaLs to B ceLLs. ImmunoL. Rev.(1997)156,39-52.
[50] Liu, Y.J., Joshua, D.E., WiLLiams, G.T., Smith, C.A., Gordon, J. and MacLennan, I.C. Mechanism of antigen-driven seLection in germinaL centres. Nature (1989)342,929-931.
[51] Liu, Y.J., Arpin, C., de BouteiLLer, O., Guret, C., Banchereau, J., Martinez-VaLdez, H. and Lebecque, S. SequentiaL triggering of apoptosis, somatic mutation and isotype switch during germinaL center deveLopment. Semin. ImmunoL. (1996)8, 169-177.
[52] MacLennan, J.C. GerminaL centers. Annu. Rev. ImmunoL. (1994)12,117-139.
[53] Hennino, A., Berard, M., Krammer, P.H. and Defrance, T. FLICE-inhibitory protein is a key reguLator of germinaL center B ceLL apoptosis. J. Exp. Med. 193(2001), 447-458.
[54] van Eijk, M., Medema, J.P. and de Groot, C. Cutting edge: ceLLuLar Fas-associated death domain-Like IL-1-converting enzyme-inhibitory protein protects germinaL center B ceLLs from apoptosis during germinaL center reactions. J. ImmunoL. (2001)166, 6473-6476.
[55] van Eijk, M., Defrance, T., Hennino, A. and de Groot, C. Death-receptor contribution to the germinaL-center reaction. Trends ImmunoL. (2001)22, 677-682.
[56] Lindhout, E., Lakeman, A. and de Groot, C. FoLLicuLar dendritic ceLLs inhibit apoptosis in human B Lymphocytes by a rapid and irreversibLe bLockade of preexisting endonucLease. J.Exp. Med. (1995)181, 1985-1995.
[57] van Eijk, M. and de Groot, C. GerminaL center B ceLL apoptosis requires both caspase and cathepsin activity. J. ImmunoL. (1999)163, 2478-2482.
[58] van Nierop, K., MuLLer, F.J., Stap, J., Van Noorden, C.J., van Eijk, M., and de Groot, C.LysosomaL destabiLization contributes to apoptosis of germinaL center B-Lymphocytes. J.Histochem. Cytochem. (2006) VoLume 54 (12): 1425-1435.
[59] van Eijk, M., Van Noorden, C.J. and de Groot, C. Proteinases and their inhibitors in the immune system. Int. Rev. CytoL. (2003)222, 197-236.
[60] LindahL, P., Abrahamson, M. and Bjork, 1. Interaction of recombinant human cystatin C with the cysteine proteinases papain and actinidin. Biochem. J. (1992)281,49-55.
[61] Abrahamson, M., Barrett, A.J., SaLvesen, G. and Grubb, A. IsoLation of six cysteine proteinase inhibitors from human urine. Their physicochemicaL and enzyme kinetic properties and concentrations in bioLogicaL fLuids. J. BioL. Chem. (1986)261,11282- 11289.
[62] Abrahamson, M., OLafsson, I., PaLsdottir, A., ULvsback, M., LundwaLL, A., Jensson, O. and Grubb, A. Structure and expression of the human cystatin C gene. Biochem. J. (1990)268,287-294.
[63] Abrahamson, M., Jonsdottir, S., OLafsson, I., Jensson, O. and Grubb, A. Hereditary cystatin C amyLoid angiopathy: identification of the disease-causing mutation and specific diagnosis by poLymerase chain reaction based anaLysis. Hum. Genet. (1992)89, 377-380.
[64] Merz, G.S., Benedikz, E., Schwenk, V., Johansen, T.E., VogeL, L.K., Rushbrook, J.L. and Wisniewski, H.M. Human cystatin C forms an inactive dimer during intraceLLuLar trafficking in transfected CHO ceLLs. J. CeLL PhysioL. (1997)173, 423-432.
[65] Huh, C.G., Hakansson, K., Nathanson, C.M., Thorgeirsson, U.P., Jonsson, N., Grubb, A.,Abrahamson, M. and KarLsson, S. Decreased metastatic spread in mice homozygous for a nuLL aLLeLe of the cystatin C protease inhibitor gene. MoL. PathoL. (1999)52, 332-340.
[66] Bengtsson, E., To, F., Hakansson, K., Grubb, A., Branen, L., NiLsson, I. and Jovinge, S. Lack of the cysteine protease inhibitor cystatin C promotes atheroscLerosis in apoLipoprotein E-deficient mice. ArterioscLer. Thromb. Vase. BioL. (2005)25, 2151-2156.
[67] Taupin, P., Ray, J., Fischer, W.H., Suhr, S.T., Hakansson, K., Grubb, A. and Gage, F.H. FGF-2-responsive neuraL stem ceLL proLiferation requires CCg, a noveL autocrine/paracrine cofactor. Neuron (2000)28, 385-397.
[68] MeLLman, I. and Steinman, R.M. Dendritic ceLLs: speciaLized and reguLated antigen processing machines. CeLL (2001)106,255-258.
[69] Hunt, D.F., MicheL, H., Dickinson, T.A., Shabanowitz, J., Cox, A.L., Sakaguchi, K., AppeLLa,E., Grey, H.M. and Sette, A. Peptides presented to the immune system by the murine cLass Ⅱ major histocompatibiLity compLex moLecuLe I-Ad. Science (1992)256, 1817-1820.
[70] Hashimoto, S., Suzuki, T., Dong, H.Y., Nagai, S., Yamazaki, N. and Matsushima, K. SeriaL anaLysis of gene expression in human monocyte-derived dendritic ceLLs. BLood (1999)94, 845-852.
[71] Zavasnik-Bergant, T., Repnik, U., Schweiger, A., Romih, R., Jeras, M., Turk, V. and Kos, J.Differentiation- and maturation-dependent content, LocaLization, and secretion of cystatin C in human dendritic ceLLs. J. Leukoc. BioL. (2005)78, 122-134.
[72] Pierre, P. and MeLLman, I. DeveLopmentaL reguLation of invariant chain proteoLysis controLs MHC cLass Ⅱ trafficking in mouse dendritic ceLLs. CeLL (1998)93, 1135-1145.
[73] EL Sukkari, D., WiLson, N.S., Hakansson, K., Steptoe, R.J., Grubb, A., Shortman,K. and ViLLadangos, J.A. The protease inhibitor cystatin C is differentiaLLy expressed among dendritic ceLL popuLations, but does not controL antigen presentation. J. ImmunoL. (2003)171,5003-5011.
[74] Kitamura, H., Kamon, H., Sawa, S., Park, S.J., Katunuma, N., Ishihara, K., Murakami, M. and Hirano, T. IL-6-STAT3 controLs intraceLLuLar MHC cLass Ⅱ aLphabeta dimer LeveL through cathepsin S activity in dendritic ceLLs. Immunity (2005)23,491-502.
[75] Edwards, A.D., ChaussabeL, D., TomLinson, S., SchuLz, O., Sher, A. and Reise Sousa, C.ReLationships among murine CD11c(high) dendritic ceLL subsets as reveaLed by baseLine gene expression patterns. J. ImmunoL. (2003)171, 47-60.
[76] Vremec, D., PooLey, J., Hochrein, H., Wu, L. and Shortman, K. CD4 and CDS expression by dendritic ceLL subtypes in mouse thymus and spLeen. J. ImmunoL. (2000)164, 2978-2986.
[77] PuLendran, B., Smith, J.L., Caspary, G., BraseL, K., Pettit, D., Maraskovsky, E. and MaLiszewski, C.R. Distinct dendritic ceLL subsets differentiaLLy reguLate the cLass of immune response in vivo. Proc. NatL Acad. Sci. USA (1999)96, 1036-1041.
[78] MaLdonado-Lopez, R., De Smedt, T., MicheL, P., Godfroid, J., Pajak, B., Heirman, C.ThieLemans, K., Leo, O., Urbain, J. and Moser, M. CD8aLpha+ and CD8aLpha-subcLasses of dendritic ceLLs direct the deveLopment of distinct T heLper ceLLs in vivo. J. Exp. Med.(1999)189,587-592.
[79] Hochrein, H., Shortman, K., Vremec, D., Scott, B., Hertzog, P. and O'Keeffe, M. DifferentiaL production of IL-12, IFNaLpha, and IFN-gamma by mouse dendritic ceLL subsets. J. ImmunoL.(2001)166,5448-5455.
[80] den Haan, J.M., Lehar, S.M. and Bevan, M.J. CD8(+) but not CD8(_) dendritic ceLLs cross-prime cytotoxic T ceLLs in vivo. J. Exp. Med. (2000)192, 1685-1696.
[81] den Haan, J.M. and Bevan, M.J. Antigen presentation to CD8+T ceLLs: cross-priming in infectious diseases. Curr. Opin. ImmunoL. (2001)13, 437-441.
[82] Heath, W.R., BeLz, G.T., Behrens, G.M, Smith, C.M., Forehan, S.P., Parish, J.A., Davey, G.M., WiLson, N.S., Carbone, F.R. and ViLLadangos, J.A. Cross-presentation, dendritic ceLL subsets, and the generation of immunity to ceLLuLar antigens. ImmunoL. Rev. (2004)199, 9-26.
[83] BeLz, G.T., Shortman, K., Bevan, M.J. and Heath, W.R. CD8aLpha+ dendritic ceLLs seLectiveLy present MHC cLass Irestricted noncytoLytic viraL and intraceLLuLar bacteriaL antigens in vivo. J. ImmunoL. (2005)175, 196-200.
[84] LaLioti, M.D., Mirotsou, M., Buresi, C., Peitsch, M.C., Rossier, C., Ouazzani, R., BaLdy-MouLinier, M., Bottani, A., MaLafosse, A. and Antonarakis, S.E. Identification of mutations in cystatin B, the gene responsibLe for the Unverricht-Lundborg type of progressive myocLonus epiLepsy (EPM1). Am. J. Hum. Genet. (1997)60, 342-351.
[85] LaLioti, M.D., Scott, H.S., Buresi, C., Rossier, C., Bottani, A., Morris, M.A., MaLafosse, A. and Antonarakis, S.E. Dodecamer repeat expansion in cystatin B gene in progressive myocLonus epiLepsy. Nature (1997)386, 847-851.
[86] Pennacchio, L.A., Lehesjoki, A.E., Stone, N.E., WiLLour, V.L., Virtaneva, K., Miao, J.,D'Amato, E., Ramirez, L., Faham, M., Koskiniemi, M., Warrington, J.A., Norio, R., de La ChapeLLe, A., Cox, D.R. and Myers, R.M. Mutations in the gene encoding cystatin B in progressive myocLonus epiLepsy (EPM1). Science (1996)271, 1731-1734.
[87] Pennacchio, L.A., BouLey, D.M., Higgins, K.M., Scott, M.P., NoebeLs, J.L. and Myers, R.M. Progressive ataxia, myocLonic epiLepsy and cerebeLLar apoptosis in cystatin B-deficient mice.Nat. Genet. (1998)20, 251-258.
[88] LieuaLLen, K., Pennacchio, L.A., Park, M., Myers, R.M. and Lennon, G.G. Cystatin B-deficient mice have increased expression of apoptosis and gLiaL activation genes. Hum. Mot Genet.(2001)10, 1867-1871.
[89] Houseweart, M.K., Pennacchio, L.A., ViLaythong, A., Peters, C., NoebeLs, J.L. and Myers,R.M. Cathepsin B but not cathepsins L or S contributes to the pathogenesis of Unverricht-Lundborg progressive myocLonus epiLepsy (EPM1). J. NeurobioL. (2003)56,315-327.
[90] Kopitar-JeraLa, N., Schweiger, A., Myers, R.M., Turk, V. and Turk, B. Sensitization of stefin B-deficient thymocytes towards staurosporin-induced apoptosis is independent of cysteine cathepsins. FEBS Lett. (2005)579, 2149-2155.
[91] BrannvaLL, K., HjeLm, H., Korhonen, L., Lahtinen, U., Lehesjoki, A.E. and LindhoLm, D. Cystatin-B is expressed by neuraL stem ceLLs and by differentiated neurons and astrocytes. Biochem. Biophys. Res. Commun. (2003)308, 369-374.
[92] Hashimoto, S., Suzuki, T., Dong, H.Y., Yamazaki, N. and Matsushima, K. SeriaL anaLysis of gene expression in human monocytes and macrophages. BLood (1999)94, 837-844.
[93] Verdot, L., LaLmanach, G., Vercruysse, V., Hartmann, S., Lucius, R., Hoebeke, J., Gauthier, F.and Vray, B. Cystatins upreguLate nitric oxide reLease from interferon-gamma-activated mouse peritoneaL macrophages. J. BioL. Chem. (1996)271, 28077-28081.
[94] Verdot, L., LaLmanach, G., Vercruysse, V., Hoebeke, J., Gauthier, F. and Vray, B. Chicken cystatin stimuLates nitric oxide reLease from interferon-gamma-activated mouse peritoneaL macrophages via cytokine synthesis. Eur. J. Biochem. (1999)266, 1111-1117.
[95] Das, L., Datta, J.N.L., Bandyopadhyay, S. and Das, P.K. SuccessfuL therapy of LethaL murine visceraL Leishmaniasis with cystatin invoLves up-reguLation of nitric oxide and a favorabLe T ceLL response. J. immunoL. (2001)166, 4020-4028.
[96] Natasa Kopitar-JeraLa. The roLe of cystatins in ceLLs of the immune system. FEBS Letters.(2006)580,6295-6301.
[97] Hartmann, S., B. Kyewski, B. Sonnenburg, and R. Lucius. A fiLariaL cysteine protease inhibitor down-reguLates T-ceLL proLiferation and enhances interLeukin-10 production. Eur. J. ImmunoL. (1997)27: 2253-2260.
[98] Scho nemeyer, A., R. Lucius, B. Sonnenburg, N. Brattig, R. Sabat, K. SchiLLing, J. BradLey,and S. Hartmann. ModuLation of human T-ceLL responses and macrophage functions by onchocystatin, a secreted protein of the fiLariaL nematode Onchocerca voLvuLus. J. ImmunoL.(2001)167:3207-3215.
[99] Manoury, B., W. F. Gregory, R. M. MaizeLs, and C. Watts. Bm-CPI-2, a cystatin homoLog secreted by the fiLariaL parasite Brugia maLayi, inhibits cLass II MHC-restricted antigen processing. Curr. BioL. (2001)11: 447-451.
[100]Pfaff, A. W., H. SchuLz-Key, P. T. SobosLay, D. W. TayLor, K. MacLennan, and W. H. Hoffmann. Litomosoides sigmodontis cystatin acts as an immunomoduLator during experimental. fiLariasis. Int. J. ParasitoL. (2002)32: 171-178.
[101] Maekawa, Y., K. Himeno, H. Ishikawa, H. Hisaeda, T. Sakai, T. Dainichi, T. Asao, R. A. Good, and N. Katunuma. Switch of CD4_ T-ceLL differentiation from Th2 to Th1 by treatment with cathepsin B inhibitor in experimentaL Leishmaniasis. J. ImmunoL. (1998)161:2120-2127.
[102]Mosmann, T. R. Properties and functions of interLeukin-10. Adv. ImmunoL. (1994)56:1-26.
[103]Korant, B., J. Brzin, and V. Turk. Cystatin, a protein inhibitor of cysteine proteinases aLters viraL protein cLeavages in infected human ceLLs. Biochem. Biophys. Res. Commun. (1985)127: 1072-1076.
[104] Fugen Li, Haejung An, Thomas A. Seymour, David W. Barnes. Rainbow trout (Oncorhynchus mykiss) cystatin C: expression in Escherichia coLi and properties of the recombinant protease inhibitor. Comparative Biochemistry and PhysioLogy Part B (2000)125: 493-502.
[105] Li, F., An, H., Seymour, T.A., Bradford, C.S., Morrissey, M.T., BaiLey, G.S., Barnes, D.W.,MoLecuLar cLoning, sequence anaLysis and expression distribution of rainbow trout (Oncorhynchus mykiss) cystatin C. J. Comp. Biochem. PhysioL. B (1998)121, 135-143.
[106] J(a|¨)rvinen M, Rinne A. Human spLeen cyteine proteinase inhibitor. Purification,fractionation into isoeLectric variants and some properties of the variants. Biochim Biophys Acta.(1982)708:210-217.
[107] Green GDJ, Kembhavi AA, Davies ME, Barrett AJ. CystatinLike cysteine proteinase inhibitors from human Liver. Biochem J.(1984)218:939-946.
[108] Abrahamson M, Barrett AJ, SaLvesen G, Grubb A. IsoLation of six cysteine proteinase inhibitors from human urine. J BioL Chem(1986)261:11282-11289.
[109] SLoane BF, Moin K, Sameni M, Tait LR, Rozhin J, ZiegLer G. Membrane association of cathepsin B can be induced by transfection of human breast epitheLiaL ceLLs with c-Haras oncogene. J CeLL Sci. (1994b) 107: 373-384.
[110] Sameni M, ELLiott E, ZiegLer G, Fortgens PH, Dennison C, SLoane BF. Cathepsins B and D are LocaLized at surface of human breast cancer ceLLs. PathoL OncoL Res (1995)1:43—53.
[111] Catharine C. CaLkins, Mansoureh Sameni, Jennifer KobLinski, Bonnie F. SLoane, and Kamiar Moin. DifferentiaL LocaLization of Cysteine Protease Inhibitors and a Target Cysteine Protease, Cathepsin B, by Immuno-ConfocaL Microscopy. The JournaL of Histochemistry & Cytochemistry,(1998) VoLume 46(6): 745-751,
[112]GosseLin EJ, Cate CC, PettengiLL OS, et aL. Immunocutochemistry: Its evoLution and criteria for its appLication in the study of epon-embedded ceLLs and tissues. Am J Anat, (1986)175:135-160.
[113]Toru Hosoi, Sawako Suzuki, and et aL. LPS induces stefin A3 expression in mouse primary cuLtured gLiaL ceLLs. MoLecuLar Brain Research (2005)140: 138-141.
[114] BeutLer, B.A. & Van HuffeL, C. (1994) UnraveLing function in the TNF Ligand and receptor famiLies. Science 264, 667?68.
[115] Howard, M., O'Garra, A., Ishida, H., de WaaL MaLefyt, R. & de Vries, J. (1992) BioLogicaL properties of interLeukin 10. J. CLin. ImmunoL. 12, 239±247.
[116] Peter Schierack, Richard Lucius, and et aL. Parasite-Specific ImmunomoduLatory Functions of FiLariaL Cystatin. Infection and Immunity, (2003) VoL. 71, No. 5,2422-2429.
[117] Marcia ALvarez-Fernandez, ALan J. Barrett and et aL. Inhibition of MammaLian Legumain by Some Cystatins Is Due to a NoveL Second Reactive Site, the JournaL of BioLogicaL Chemistry. (1999) VoL. 274, No. 27, Issue of JuLy 2, pp. 19195-19203.
[118] 马冬梅 一， 白俊杰， 劳海华等。中华鲟半胱氨酸蛋白酶抑制剂C基因的原核表达。(2003)VoL．27，No．3，239-244。