Toll样受体2、4、9mRNA在带状疱疹患者外周血单个核细胞中的表达及意义
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摘要
目的研究带状疱疹患者外周血单个核细胞中Toll样受体(TLR) TLR2、4、9mRNA的表达情况,并探讨其与带状疱疹的发病关系。方法采用SYBER Green I实时定量PCR方法检测30例带状疱疹患者和20例正常人的外周血单一核细胞中TLR2、TLR4、TLR9mRNA的表达水平。结果带状疱疹患者与正常人对照,其外周血单一核细胞中TLR2、TLR4、TLR9mRNA的表达水平均明显升高,其中TLR2(t=2.23,P=0.031),TLR4(t=2.32,P=0.028),TLR9(t=2.27,P=0.031),具有统计学差异(P<0.05)。结论带状疱疹患者外周血单一核细胞中TLR2、TLR4、TLR9mRNA的表达水平都明显升高,推测：在带状疱疹患者的发病过程中,TLR2、TLR4、TLR9mRNA可能参与了水痘-带状疱疹病毒的识别及抗病毒免疫。
Objective To study the expression of TLR2,4,9mRNA in peripheral blood mononuclear cells (PBMC) of patients with herpes zoster, the relation between TLR and herpes zoster was discussed. Methods The expression of TLR2,4,9mRNA were detected by real-time quantitative PCR(RT-PCR) in 30 patients and 20 healthy individuals control group respectively. Rusults The experimental of TLR2,4,9mRNA were clearly higher than the healthy control group, and TLR2 (t=2.23, P=0.031), TLR4 (t=2.32, P=0.028), TLR9(t=2.27, P=0.031), the differences were statistically significant (p<0.05). Conclusion The high expression of TLR2,4,9mRNA showed that they may take part in the recognition of Varicella-zoster virus and antivirus immunity.
Objective To study the expression of TLR2,4,9mRNA in peripheral blood mononuclear cells (PBMC) of patients with herpes zoster, the relation between TLR and herpes zoster was discussed. Methods The expression of TLR2,4,9mRNA were detected by real-time quantitative PCR(RT-PCR) in 30 patients and 20 healthy individuals control group respectively. Rusults The experimental of TLR2,4,9mRNA were clearly higher than the healthy control group, and TLR2 (t=2.23, P=0.031), TLR4 (t=2.32, P=0.028), TLR9(t=2.27, P=0.031), the differences were statistically significant (p<0.05). Conclusion The high expression of TLR2,4,9mRNA showed that they may take part in the recognition of Varicella-zoster virus and antivirus immunity.
引文
[1]魏爱华,刘永,尹晓慧,等.带状疱疹患者细胞免疫功能的检测及意义[J].中国麻风皮肤病杂志.2006,03(22)：234.
[2]张炜综述.带状疱疹病毒致病性和防治的研究进展.国外医学皮肤病学分册.1996,22：257.
[3]郭淑兰,孙青,李诚菊,等.带状疱疹患者细胞免疫功能的测定.临床皮肤科杂志.1999,28(1)：25
[4]何凤莲,张妍蓓.Toll样受体的研究进展[J].国际呼吸杂志,2006,26(9)：655-659.
[5]Vives PM, Somoza N, Fernandez-Alvarez [J], et al. Evidence of expression of endotoxin receptors CD14, Toll-like receptors TLR4 and TLR2 and associated molecule MD-2 and of sensitivity to endotoxin (LPS) in islet beta cells. J Clin Exp Immunol,2003,133 (2):208-218.
[6]Modlin DH, Kiss-Toth E, Visintin A, et al. Evidence for an accessory protein f unction for Toll-like receptor 1 in anti-bacterial responses. J Immunol,2000,165: 7125-7132.
[7]王平忠,白雪帆.Toll样受体介导的抗病毒天然免疫.细胞与分子免疫学杂志,2008,24(5)：、539-541.
[8]冯悦.病毒相关Toll样受体研究进展[J].现代免疫学.2007,27(5)：434-438.
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[13]Hashimoto M, Asai Y, Ogawa T, et al. Separation and structural analysis of li poprotein in a lipopolysaccharide preparation from porphyromonas gingivalis. Int Immunol,2004,16 (10):1431-1437.
[14]Mirlashari MR, Lyberg T. Expression and involvement of Toll-like receptors T LR2, TLR4 and CD 14 in monocyte TNF-alpha production induced by lipopoly saccharides from Neisseria meningitidis.J Med Sci Monit,2003,9(8):316-324.
[15]Mukhopadhyay S, Herre J, Brown GD, et al. The potential for Toll-like recepto rs to collaborate with other innate immune receptors[J]. Immunology,2004,112 (4):521-530.
[16]Kaisho T, Akira S. Toll-like receptors as adjurant receptors.J Biochim Biophys Acta,2002,1598(1):1-13.
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[18]HornungV, Rothenfusser S, Britsch S, et al. Quantitative expression of toll-like r eceptor 1-10mRNA in cellular subsets of human peripheral blood mononuclearce lls and sensitivity to CpG oligdeoxynucleotides. J Immunol,2002,168(9):4531-4537.
[19]Kohllisch G, Kalali BN, Voelcker V, et al. Various members of the Toll-like re ceptor family contribute to the innate immune response of human epidermal ker atinocytes[J]. Immunology,2005,114(4):531-541.
[20]Compton T, Kurt-Jones EA, Boehme KW, et al. Human cytomegalovirus activat es inflammatory cytokine responses via CD 14 and Toll-like receptor 2[J]. J Viro 1,2003,77 (8):4588-4596.
[21]Kurt-Jones EA, Popova L, Kwinn L, et al. Pattern recognition receptors TLR4 a nd CD 14 mediate response to respiratory syncytial virus[J]. Nat Immunol,2000, 1 (5):398-401.
[22]Chatelhers, Kotbm. Preferential stimulation of human lymphocytes by oligodeoxy nucleotides that copy DNA CpG motifs present in virulent genes ofgroupA strept ococci[J]. Eur J Immunol,2000,30(4):993-1001.
[23]Lund J, Sato A, Akira S, et al. Toll-like receptor 9-mediated recognition of Her pes simplex virus-2 by plasmacytoid dendritic cells[J]. Exp Med,2003,198 (3): 513-520.
[24]Krug A, Luker GD, Barchet W, et al. Herpes simplex virus type 1 activates mu rine natural interferon producing cells through toll-like receptor 9[J]. Blood,2004, 103 (4):1433-1437.
[25]徐配红,袁定芬等.生殖器疱疹患者外周血单个核细胞TLR9的表达及血清IL-12、IFN-γ水平的研究.诊断学理论与实践,2007,6(4)：366-368.
[26]Akira S, Takeda K. Toll-like receptor signalling[J]. Nat Rev Immunol,2004, 4(7):499-511.
[27]Borregaard N, Theilgaard-Mohnch K, Cowland JB, et al. Neutrophils and keratin ocytes in innate immunity--cooperative actions to provide antimicrobial defense at the right time and place[J].J Leukoc Biol,2005,77(4):439-443.
[1]Vives PM, Somoza N, Fernandez-Alvarez J, et al.Evidence of expression of endo toxin receptors CD 14, Toll-like receptors TLR4 and TLR2 and associated molecul e MD-2 and of sensitivity to endotoxin (LPS) in islet beta cells. J Clin Exp Im munol,2003,133(2):208-218.
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[3]冯悦.病毒相关Toll样受体研究进展[J].现代免疫学,2007,27(5)：434-438.
[4]Ahmad N, Hacker H, Rutzm P, et al. Bacterial CpG-DNA and lipoploysacchari des activate Toll-like receptors at distinct cellular compartments[J]. Eur J lmmuno 1,2002,32 (3):1958-1968.
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[13]Sarkar SN, Smith HL, Rowe TM, et al.Double-stranded RNA signaling by To 11-like receptor 3 requires specific tyrosine residues in its cytoplasmic domain [J].J Biol Chem,2003,278 (7):4398-4396.
[14]Sun R, Gao B. Negative regulation of liver regeneration by innate immunity (n atural killer cells/interferon-gamma) [J]. Gastroenterology,2004,127(5):1525-153 9.
[15]Matsumoto M, Funami K, Oshiumi H, et al. Toll-like receptor 3:a link betwee n toll-like receptor, interferon and viruses[J]. Microbiol Immunol,2004,48 (3): 147-154.
[16]Li K, Foy E, Ferreon JC, et al.Immune evasion by hepatitis C virus NS3/4 pr otease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF [J]. Pr oc Natl Acad Sci USA,2005,102 (8):2992-2997.
[17]SchulzO, Diebold SS, ChenM,et al. Toll-like receptor 3 promotes cross-priming to virus-infected cells[J].Nature,2005,433(7082):887-892.
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[2]张炜综述.带状疱疹病毒致病性和防治的研究进展.国外医学皮肤病学分册.1996,22：257.
[3]郭淑兰,孙青,李诚菊,等.带状疱疹患者细胞免疫功能的测定.临床皮肤科杂志.1999,28(1)：25
[4]何凤莲,张妍蓓.Toll样受体的研究进展[J].国际呼吸杂志,2006,26(9)：655-659.
[5]Vives PM, Somoza N, Fernandez-Alvarez [J], et al. Evidence of expression of endotoxin receptors CD14, Toll-like receptors TLR4 and TLR2 and associated molecule MD-2 and of sensitivity to endotoxin (LPS) in islet beta cells. J Clin Exp Immunol,2003,133 (2):208-218.
[6]Modlin DH, Kiss-Toth E, Visintin A, et al. Evidence for an accessory protein f unction for Toll-like receptor 1 in anti-bacterial responses. J Immunol,2000,165: 7125-7132.
[7]王平忠,白雪帆.Toll样受体介导的抗病毒天然免疫.细胞与分子免疫学杂志,2008,24(5)：、539-541.
[8]冯悦.病毒相关Toll样受体研究进展[J].现代免疫学.2007,27(5)：434-438.
[9]Ahmad N, Hacker H, Rutzm P, et al. Bacterial CpG-DNA and lipoploysacchar ides activate Toll-like receptors at distinct cellular compartments [J]. Eur J lmmu nol,2002,32 (3):1958-1968.
[10]O'Neill LA. After the toll rush[J]. Science,2004,303(5663):1481-1482.
[11]Akira S, Hemmi H. Recognition of pathogen-associated molecular patterns by TL R family[J]. Immunol Lett,2003,85:85-95.
[12]Heumann D, Roger T. Initial responses to endotoxins and Gram-negative bacteria. J Clin Chim Acta,2002,323(1-2):59-72.
[13]Hashimoto M, Asai Y, Ogawa T, et al. Separation and structural analysis of li poprotein in a lipopolysaccharide preparation from porphyromonas gingivalis. Int Immunol,2004,16 (10):1431-1437.
[14]Mirlashari MR, Lyberg T. Expression and involvement of Toll-like receptors T LR2, TLR4 and CD 14 in monocyte TNF-alpha production induced by lipopoly saccharides from Neisseria meningitidis.J Med Sci Monit,2003,9(8):316-324.
[15]Mukhopadhyay S, Herre J, Brown GD, et al. The potential for Toll-like recepto rs to collaborate with other innate immune receptors[J]. Immunology,2004,112 (4):521-530.
[16]Kaisho T, Akira S. Toll-like receptors as adjurant receptors.J Biochim Biophys Acta,2002,1598(1):1-13.
[17]Kaisho T, Akira S. Pleiotropic function of Toll-like receptors. Microbes Infect,2 004,6(15):1388-1394.
[18]HornungV, Rothenfusser S, Britsch S, et al. Quantitative expression of toll-like r eceptor 1-10mRNA in cellular subsets of human peripheral blood mononuclearce lls and sensitivity to CpG oligdeoxynucleotides. J Immunol,2002,168(9):4531-4537.
[19]Kohllisch G, Kalali BN, Voelcker V, et al. Various members of the Toll-like re ceptor family contribute to the innate immune response of human epidermal ker atinocytes[J]. Immunology,2005,114(4):531-541.
[20]Compton T, Kurt-Jones EA, Boehme KW, et al. Human cytomegalovirus activat es inflammatory cytokine responses via CD 14 and Toll-like receptor 2[J]. J Viro 1,2003,77 (8):4588-4596.
[21]Kurt-Jones EA, Popova L, Kwinn L, et al. Pattern recognition receptors TLR4 a nd CD 14 mediate response to respiratory syncytial virus[J]. Nat Immunol,2000, 1 (5):398-401.
[22]Chatelhers, Kotbm. Preferential stimulation of human lymphocytes by oligodeoxy nucleotides that copy DNA CpG motifs present in virulent genes ofgroupA strept ococci[J]. Eur J Immunol,2000,30(4):993-1001.
[23]Lund J, Sato A, Akira S, et al. Toll-like receptor 9-mediated recognition of Her pes simplex virus-2 by plasmacytoid dendritic cells[J]. Exp Med,2003,198 (3): 513-520.
[24]Krug A, Luker GD, Barchet W, et al. Herpes simplex virus type 1 activates mu rine natural interferon producing cells through toll-like receptor 9[J]. Blood,2004, 103 (4):1433-1437.
[25]徐配红,袁定芬等.生殖器疱疹患者外周血单个核细胞TLR9的表达及血清IL-12、IFN-γ水平的研究.诊断学理论与实践,2007,6(4)：366-368.
[26]Akira S, Takeda K. Toll-like receptor signalling[J]. Nat Rev Immunol,2004, 4(7):499-511.
[27]Borregaard N, Theilgaard-Mohnch K, Cowland JB, et al. Neutrophils and keratin ocytes in innate immunity--cooperative actions to provide antimicrobial defense at the right time and place[J].J Leukoc Biol,2005,77(4):439-443.
[1]Vives PM, Somoza N, Fernandez-Alvarez J, et al.Evidence of expression of endo toxin receptors CD 14, Toll-like receptors TLR4 and TLR2 and associated molecul e MD-2 and of sensitivity to endotoxin (LPS) in islet beta cells. J Clin Exp Im munol,2003,133(2):208-218.
[2]王平忠,白雪帆,等.Toll样受体介导的抗病毒天然免疫.细胞与分子免疫学杂志,2008,24(5)：539-541.
[3]冯悦.病毒相关Toll样受体研究进展[J].现代免疫学,2007,27(5)：434-438.
[4]Ahmad N, Hacker H, Rutzm P, et al. Bacterial CpG-DNA and lipoploysacchari des activate Toll-like receptors at distinct cellular compartments[J]. Eur J lmmuno 1,2002,32 (3):1958-1968.
[5]Steward R, McNally FJ, Schedl P, et al. Isolation of the dorsal locus of Drosop hila[J]. Nature,1984,311 (5983):262-265.
[6]Medzhitov R,Preston-Hurlburt P,Janeway CA Jr, et al. A human homologue of th e Drosophila Toll protein signals activation of adaptive immunity [J]. Nature,199 7,388(6640):394-397.
[7]Matsumoto M, Funami K, Tanabe M, et al. Subcellular localization of Toll-like r eceptor 3 in human dendritic cells [J]. J Immunol,2003,171 (9):3154-3162.
[8]Akira S, Hemmi H. Recognition of pathogen-associated molecular patterns by TL R family[J]. Immunol Lett,2003,85:85-95.
[9]ComptonT, Kurt-JonesEA, BoehmeKW, etal. Human cytomegalo-virus activates in flammatory cytokine responsesviaCD14 and Toll-like receptor2[J].J Virol,2003,7 7(8):4588-4596.
[10]BoehmeKW, Singh J, Perry ST,etal. Human cytomegalovirus elic its a coordinat ed cellular antiviral responseviaenvelope glycoprotein B[J].J Virol,2004,78(3): 1202-1211.
[11]Kurt-JonesEA, ChanM, Zhou S,etal. Herpes simplex virus 1 interaction with Tol 1-like receptor 2 contributes to lethal encephalitis [J].ProcNatlAcad SciUSA,200 4,101(5):1315-1320.
[12]Rehli M. Of mice arid men:species variations of Toll-like receptor expression [J].Trends Immunol,2002,23 (8):375-378.
[13]Sarkar SN, Smith HL, Rowe TM, et al.Double-stranded RNA signaling by To 11-like receptor 3 requires specific tyrosine residues in its cytoplasmic domain [J].J Biol Chem,2003,278 (7):4398-4396.
[14]Sun R, Gao B. Negative regulation of liver regeneration by innate immunity (n atural killer cells/interferon-gamma) [J]. Gastroenterology,2004,127(5):1525-153 9.
[15]Matsumoto M, Funami K, Oshiumi H, et al. Toll-like receptor 3:a link betwee n toll-like receptor, interferon and viruses[J]. Microbiol Immunol,2004,48 (3): 147-154.
[16]Li K, Foy E, Ferreon JC, et al.Immune evasion by hepatitis C virus NS3/4 pr otease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF [J]. Pr oc Natl Acad Sci USA,2005,102 (8):2992-2997.
[17]SchulzO, Diebold SS, ChenM,et al. Toll-like receptor 3 promotes cross-priming to virus-infected cells[J].Nature,2005,433(7082):887-892.
[18]Rassa JC, Meyers JL, ZhangY,et al. Murine retroviruses activate B cellsviaintera ction with Toll-like receptor 4[J]. Proc Natl Acad Sci USA,2002,99(4):2281-2286.
[19]Burzyn D, Rassa JC, Kim D,et al. Toll-like receptor 4-dependent activation of dendritic cells by a retrovirus[J].J Virol,2004,78(2):576-584.
[20]Kurt-JonesEA, Popova L, Kwinn L,etal. Pattern recognition receptorsTLR4 and CD14 mediate response to respiratory syncytial virus [J].Nat Immunol,2000,1 (5):398-401.
[21]Diebold SS, KaishoT, HemmiH,etal. Innate antiviral responses by means of TLR 7-mediated recognition of single-stranded RNA [J]. Science,2004,303(5663):1 529-1531.
[22]HeilF, HemmiH, HochreinH, etal. Species-specific recognition of single-stranded RNA viatoll-like receptor7 and 8[J]. Science,2004,303(5663):1526-1529.
[23]Diebold SS, MassacrierC, Akira S, et al. Nucleic acid agonists for toll-like recep tor7 are defined by the presence ofuridine ribonucleotides[J]. Eur J Immunol,2 006,36(12):3256-3267.
[24]Edwards AD, Iebold SS, Slack EC, et al. Toll-like receptor expression in murin e DC subsets:lack of TLR7 expression by CD8a+DC correlates with unresponsi veness to imidazoquinolines[J].Eur J Immunol,2003,33 (4):827-833.
[25]JurkM, HeilF, Vollmer J,et al. Human TLR7 or TLR8 independently confer resp onsiveness to the antiviral compound R-848[J]. Nat Immunol,2002,3(2):196-20 0.
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