IL-8与自身免疫性肝病的关系
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摘要
IL-8是一种具有趋化作用的炎性细胞因子,在自身免疫性肝病中的表达水平明显升高,且能够与其相应受体——趋化因子受体1、趋化因子受体2结合,进而发挥促炎性细胞趋化、促血管生成、促纤维化和诱导细胞增殖的作用,参与疾病进程。综述了IL-8与自身免疫性肝病的相关研究进展。
Interleukin-8( IL-8) is an inflammatory cytokine with chemotaxis and there is a significant increase in the expression of IL-8 in autoimmune liver diseases. It participates in disease progression by binding to its receptors CXCR1 and CXCR2,promoting chemotaxis of inflammatory cells,angiogenesis,and fibrosis,and inducing cell proliferation. This article reviews the research advances in the association between IL-8 and autoimmune liver diseases.
Interleukin-8( IL-8) is an inflammatory cytokine with chemotaxis and there is a significant increase in the expression of IL-8 in autoimmune liver diseases. It participates in disease progression by binding to its receptors CXCR1 and CXCR2,promoting chemotaxis of inflammatory cells,angiogenesis,and fibrosis,and inducing cell proliferation. This article reviews the research advances in the association between IL-8 and autoimmune liver diseases.
引文
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[2]ZIMMERMANN H,SEIDLER S,GASSLER N,et al.Interleukin-8is activated in patients with chronic liver diseases and associated with hepatic macrophage accumulation in human liver fibrosis[J].PLo S One,2011,6(6):e21381.
[3]MOTOO Y,XIE M,MOURI H,et al.Expression of interleukin-8in human obstructive pancreatitis[J].JOP,2004,5(3):138-144.
[4]CARRP,MORTENSON R,KING T,et al.Increased expression of the interleukin-8 gene by alveolar macrophages in idiopathic pulmonary fibrosis.A potential mechanism for the recruitment and activation of neutrophils in lung fibrosis[J].JClin Invest,1991,88(6):1802-1810.
[5]WANG H,WANG QJ,SUN FB,et al.Effect of entecavir combined with Fuzheng Huayu capsules on inflammatory factors and fibrosis markers in patients with compensated chronic hepatitis B-related cirrhosis[J].J Clin Hepatol,2016,32(9):1734-1738.(in Chinese)王贺,王千钧,孙风波,等.恩替卡韦联合扶正化瘀胶囊对代偿期慢性乙型肝炎肝硬化患者炎性因子及纤维化指标的影响[J].临床肝胆病杂志,2016,32(9):1734-1738.
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[10]LOHSE A,MIELI-VERGANI G.Autoimmune hepatitis[J].JHepatol,2011,55(1):171-182.
[11]LANDI A,WEISMULLER T,LANKISCH T,et al.Differential serum levels of eosinophilic eotaxins in primary sclerosing cholangitis,primary biliary cirrhosis,and autoimmune hepatitis[J].J Interferon Cytokine Res,2014,34(3):204-214.
[12]BUNCHORNTAVAKUL C,REDDY K.Diagnosis and management of overlap syndromes[J].Clin Liver Dis,2015,19(1):81-97.
[13]LIBERAL R,GRANT C.Cirrhosis and autoimmune liver disease:Current understanding[J].World J Hepatol,2016,8(28):1157-1168.
[14]LONGHI M,MA Y,MIELI-VERGANI G,et al.Adaptive immunity in autoimmune hepatitis[J].Dig Dis,2010,28(1):63-69.
[15]MONTANO-LOZA A,CZAJA A.Cell mediators of autoimmune hepatitis and their therapeutic implications[J].Dig Dis Sci,2015,60(6):1528-1542.
[16]BAIER J,MATTNER J.Mechanisms of autoimmune liver disease[J].Discov Med,2014,18(100):255-263.
[17]AKBEROVA D,KIASSOV A,ABDULGANIEVA D.Serum cytokine levels and their relation to clinical features in patients with autoimmune liver diseases[J].J Immunol Res,2017,2017:9829436.
[18]YANG M,HUANG FL,FU HT,et al.Expressions and clinical significances of IL-8 and its receptors(CXCR1/2)in peripheral blood from the patients with primary biliary cirrhosis[J].Chin J Clin Lab Sci,2014,32(5):362-365.(in Chinese)杨敏,黄凤楼,傅海涛,等.原发性胆汁性肝硬化患者外周血IL-8及其受体CXCR1、CXCR2的表达及临床意义[J].临床检验杂志,2014,32(5):362-365.
[19]TACKE F,ZIMMERMANN H,TRAUTWEIN C,et al.CXCL5plasma levels decrease in patients with chronic liver disease[J].J Gastroenterol Hepatol,2011,26(3):523-529.
[20]ISSE K,HARADA K,NAKANUMA Y.IL-8 expression by biliary epithelial cells is associated with neutrophilic infiltration and reactive bile ductules[J].Liver Int,2007,27(5):672-680.
[21]YOKOYAMA T,KOMORI A,NAKAMURA M,et al.Human intrahepatic biliary epithelial cells function in innate immunity by producing IL-6 and IL-8 via the TLR4-NF-kappaB and-MAPKsignaling pathways[J].Liver Int,2006,26(4):467-476.
[22]YOKOMURO S,LUNZ J,SAKAMOTO T,et al.The effect of interleukin-6(IL-6)/gp130 signalling on biliary epithelial cell growth,in vitro[J].Cytokine,2000,12(6):727-730.
[23]UMEMURA T,SEKIGUCHI T,JOSHITA S,et al.Association between serum soluble CD14 and IL-8 levels and clinical outcome in primary biliary cholangitis[J].Liver Int,2017,37(6):897-905.
[24]Chinese Society of Hepatology,Chinese Medical Association;Chinese Society of Gastroenterology,Chinese Medical Association;Chinese Society of Infectious Diseases,Chinese Medical Association.Consensus on the diagnosis and management of primary sclerosing cholangitis(2015)[J].J Clin Hepatol,2016,32(1):23-31.(in Chinese)中华医学会肝病学分会,中华医学会消化病学分会,中华医学会感染病学分会.原发性硬化性胆管炎诊断和治疗专家共识(2015)[J].临床肝胆病杂志,2016,32(1):23-31.
[25]BANSAL A,THOMSON A,STEADMAN C,et al.Serum levels of interleukins 8 and 10,interferon gamma,granulocytemacrophage colony stimulating factor and soluble CD23 in patients with primary sclerosing cholangitis[J].Autoimmunity,1997,26(4):223-229.
[26]TABIBIAN J,O'HARA S,SPLINTER P,et al.Cholangiocyte senescence by way of N-ras activation is a characteristic of primary sclerosing cholangitis[J].Hepatology,2014,59(6):2263-2275.
[27]VESTERHUS M,HOLM A,HOV J,et al.Novel serum and bile protein markers predict primary sclerosing cholangitis disease severity and prognosis[J].J Hepatol,2017,66(6):1214-1222.
[28]ZWEERS S,SHIRYAEV A,KOMUTA M,et al.Elevated interleukin-8 in bile of patients with primary sclerosing cholangitis[J].Liver Int,2016,36(9):1370-1377.
[29]MORLAND C,FEAR J,JOPLIN R,et al.Inflammatory cytokines stimulate human biliary epithelial cells to express interleukin-8 and monocyte chemotactic protein-1[J].Biochem Soc Trans,1997,25(2):232s.
[30]AMURA C,BRODSKY K,GITOMER B,et al.CXCR2 agonists in ADPKD liver cyst fluids promote cell proliferation[J].Am JPhysiol Cell Physiol,2008,294(3):c786-c796.
[2]ZIMMERMANN H,SEIDLER S,GASSLER N,et al.Interleukin-8is activated in patients with chronic liver diseases and associated with hepatic macrophage accumulation in human liver fibrosis[J].PLo S One,2011,6(6):e21381.
[3]MOTOO Y,XIE M,MOURI H,et al.Expression of interleukin-8in human obstructive pancreatitis[J].JOP,2004,5(3):138-144.
[4]CARRP,MORTENSON R,KING T,et al.Increased expression of the interleukin-8 gene by alveolar macrophages in idiopathic pulmonary fibrosis.A potential mechanism for the recruitment and activation of neutrophils in lung fibrosis[J].JClin Invest,1991,88(6):1802-1810.
[5]WANG H,WANG QJ,SUN FB,et al.Effect of entecavir combined with Fuzheng Huayu capsules on inflammatory factors and fibrosis markers in patients with compensated chronic hepatitis B-related cirrhosis[J].J Clin Hepatol,2016,32(9):1734-1738.(in Chinese)王贺,王千钧,孙风波,等.恩替卡韦联合扶正化瘀胶囊对代偿期慢性乙型肝炎肝硬化患者炎性因子及纤维化指标的影响[J].临床肝胆病杂志,2016,32(9):1734-1738.
[6]MURPHY P.The molecular biology of leukocyte chemoattractant receptors[J].Annu Rev Immunol,1994,12(1):593-633.
[7]BALKWILL F.Cancer and the chemokine network[J].Nat Rev Cancer,2004,4(7):540-550.
[8]MURPHY P.Neutrophil receptors for interleukin-8 and related CXC chemokines[J].Semin Hematol,1997,34(4):311-318.
[9]AHUJA S,MURPHY P.The CXC chemokines growth-regulated oncogene(GRO)alpha,GRObeta,GROgamma,neutrophil-activating peptide-2,and epithelial cell-derived neutrophil-activating peptide-78 are potent agonists for the type B,but not the type A,human interleukin-8 receptor[J].J Biol Chem,1996,271(34):20545-20550.
[10]LOHSE A,MIELI-VERGANI G.Autoimmune hepatitis[J].JHepatol,2011,55(1):171-182.
[11]LANDI A,WEISMULLER T,LANKISCH T,et al.Differential serum levels of eosinophilic eotaxins in primary sclerosing cholangitis,primary biliary cirrhosis,and autoimmune hepatitis[J].J Interferon Cytokine Res,2014,34(3):204-214.
[12]BUNCHORNTAVAKUL C,REDDY K.Diagnosis and management of overlap syndromes[J].Clin Liver Dis,2015,19(1):81-97.
[13]LIBERAL R,GRANT C.Cirrhosis and autoimmune liver disease:Current understanding[J].World J Hepatol,2016,8(28):1157-1168.
[14]LONGHI M,MA Y,MIELI-VERGANI G,et al.Adaptive immunity in autoimmune hepatitis[J].Dig Dis,2010,28(1):63-69.
[15]MONTANO-LOZA A,CZAJA A.Cell mediators of autoimmune hepatitis and their therapeutic implications[J].Dig Dis Sci,2015,60(6):1528-1542.
[16]BAIER J,MATTNER J.Mechanisms of autoimmune liver disease[J].Discov Med,2014,18(100):255-263.
[17]AKBEROVA D,KIASSOV A,ABDULGANIEVA D.Serum cytokine levels and their relation to clinical features in patients with autoimmune liver diseases[J].J Immunol Res,2017,2017:9829436.
[18]YANG M,HUANG FL,FU HT,et al.Expressions and clinical significances of IL-8 and its receptors(CXCR1/2)in peripheral blood from the patients with primary biliary cirrhosis[J].Chin J Clin Lab Sci,2014,32(5):362-365.(in Chinese)杨敏,黄凤楼,傅海涛,等.原发性胆汁性肝硬化患者外周血IL-8及其受体CXCR1、CXCR2的表达及临床意义[J].临床检验杂志,2014,32(5):362-365.
[19]TACKE F,ZIMMERMANN H,TRAUTWEIN C,et al.CXCL5plasma levels decrease in patients with chronic liver disease[J].J Gastroenterol Hepatol,2011,26(3):523-529.
[20]ISSE K,HARADA K,NAKANUMA Y.IL-8 expression by biliary epithelial cells is associated with neutrophilic infiltration and reactive bile ductules[J].Liver Int,2007,27(5):672-680.
[21]YOKOYAMA T,KOMORI A,NAKAMURA M,et al.Human intrahepatic biliary epithelial cells function in innate immunity by producing IL-6 and IL-8 via the TLR4-NF-kappaB and-MAPKsignaling pathways[J].Liver Int,2006,26(4):467-476.
[22]YOKOMURO S,LUNZ J,SAKAMOTO T,et al.The effect of interleukin-6(IL-6)/gp130 signalling on biliary epithelial cell growth,in vitro[J].Cytokine,2000,12(6):727-730.
[23]UMEMURA T,SEKIGUCHI T,JOSHITA S,et al.Association between serum soluble CD14 and IL-8 levels and clinical outcome in primary biliary cholangitis[J].Liver Int,2017,37(6):897-905.
[24]Chinese Society of Hepatology,Chinese Medical Association;Chinese Society of Gastroenterology,Chinese Medical Association;Chinese Society of Infectious Diseases,Chinese Medical Association.Consensus on the diagnosis and management of primary sclerosing cholangitis(2015)[J].J Clin Hepatol,2016,32(1):23-31.(in Chinese)中华医学会肝病学分会,中华医学会消化病学分会,中华医学会感染病学分会.原发性硬化性胆管炎诊断和治疗专家共识(2015)[J].临床肝胆病杂志,2016,32(1):23-31.
[25]BANSAL A,THOMSON A,STEADMAN C,et al.Serum levels of interleukins 8 and 10,interferon gamma,granulocytemacrophage colony stimulating factor and soluble CD23 in patients with primary sclerosing cholangitis[J].Autoimmunity,1997,26(4):223-229.
[26]TABIBIAN J,O'HARA S,SPLINTER P,et al.Cholangiocyte senescence by way of N-ras activation is a characteristic of primary sclerosing cholangitis[J].Hepatology,2014,59(6):2263-2275.
[27]VESTERHUS M,HOLM A,HOV J,et al.Novel serum and bile protein markers predict primary sclerosing cholangitis disease severity and prognosis[J].J Hepatol,2017,66(6):1214-1222.
[28]ZWEERS S,SHIRYAEV A,KOMUTA M,et al.Elevated interleukin-8 in bile of patients with primary sclerosing cholangitis[J].Liver Int,2016,36(9):1370-1377.
[29]MORLAND C,FEAR J,JOPLIN R,et al.Inflammatory cytokines stimulate human biliary epithelial cells to express interleukin-8 and monocyte chemotactic protein-1[J].Biochem Soc Trans,1997,25(2):232s.
[30]AMURA C,BRODSKY K,GITOMER B,et al.CXCR2 agonists in ADPKD liver cyst fluids promote cell proliferation[J].Am JPhysiol Cell Physiol,2008,294(3):c786-c796.