趋化因子与非酒精性脂肪性肝病的相关性
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摘要
近年来,非酒精性脂肪性肝病(NAFLD)的发病率持续攀升,发病年龄呈现低龄化趋势,已成为21世纪重大的公共卫生问题之一。综述了近年部分趋化因子(CCL2、CCL5、CXCL8和CXCL10)与NAFLD的相关性研究,以期为NAFLD的发病机制及防治研究提供方向。
In recent years,the incidence rate of nonalcoholic fatty liver disease( NAFLD) keeps increasing,and the age of onset tends to become younger. NAFLD has become one of the major public health problems in the 21 st century. This article reviews the research advances in the association between some chemokines( CCL2,CCL5,CXCL8,and CXCL10) and NAFLD in recent years,in order to provide directions for the research on the pathogenesis and prevention and treatment of NAFLD.
In recent years,the incidence rate of nonalcoholic fatty liver disease( NAFLD) keeps increasing,and the age of onset tends to become younger. NAFLD has become one of the major public health problems in the 21 st century. This article reviews the research advances in the association between some chemokines( CCL2,CCL5,CXCL8,and CXCL10) and NAFLD in recent years,in order to provide directions for the research on the pathogenesis and prevention and treatment of NAFLD.
引文
[1]BOUCHRA E.Potential role of chemokines in fracture repair[J].Front Endocrinol(Lausanne),2017,8:39.
[2]WASMUTH HE,TACKE F,TRAUTWEIN C.Chemokines in liver inflammation and fibrosis[J].Semin Liver Dis,2010,30(3):215-225.
[3]FAHEY S,DEMPSEY E,LONG A.The role of chemokines in acute and chronic hepatitis C infection[J].Cell Mol Immunol,2014,11(1):25-40.
[4]MARRA F,TACKE F.Roles for chemokines in liver disease[J].Gastroenterology,2014,147(3):577-594.e1.
[5]EHOLING J,TACKE F.Role of chemokine pathways in hepatobiliary cancer[J].Cancer Lett,2016,379(2):173-183.
[6]EGAN CE,DAUGHERITY EK,ROGERS AB,et al.CCR2 and CD44 promote inflammatory cell recruitment during fatty liver formation in a lithogenic diet fed mouse model[J].PLo S One,2013,8(6):e65247.
[7]KIROVSKI G,DORN C,HUBER H,et al.Elevated systemic monocyte chemoattractrant protein-1 in hepatic steatosis without significant hepatic inflammation[J].Exp Mol Pathol,2011,91(3):780-783.
[8]SIERRA-FILARDI E,NIETO C,DOMNGUEZ-SOTO A,et al.CCL2 shapes macrophage polarization by GM-CSF and M-CSF:Identification of CCL2/CCR2-dependent gene expression profile[J].Immunol,2014,192(8):3858-3867.
[9]BAECK C,WEI X,BARTNECK M,et al.Pharmacological inhibition of the chemokine C-C motif chemokine ligand 2(monocyte chemoattractant protein 1)accelerates liver fibrosis regression by suppressing Ly-6C(+)macrophage infiltration in mice[J].Hepatology,2014,59(3):1060-1072.
[10]MIURA K,YANG L,van ROOIJEN N,et al.Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through CCR2[J].Am J Physiol Gastrointest Liver Physiol,2012,302(11):g1310-g1321.
[11]CRANFORD TL,ENOS RT,VELAZQUEZ KT,et al.Role of MCP-1 on inflammatory processes and metabolic dysfunction following high-fat feedings in the FVB/N strain[J].Int JObes(Lond),2015,40(5):844-851.
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[13]RICHARD P,WESTON CJ,ZHENHUA M,et al.CC chemokine receptor 2 promotes recruitment of myeloid cells associated with insulin resistance in nonalcoholic fatty liver disease[J].Am J Physiol Gastrointest Liver Physiol,2018,314(4):g483-g493.
[14]ERIC L,GRAEME M,RAN R,et al.Antifibrotic effects of the dual CCR2/CCR5 antagonist cenicriviroc in animal models of liver and kidney fibrosis[J].PLo S One,2016,11(6):e0158156.
[15]FRIEDMAN SL,RATZIU V,HARRISON SA,et al.A randomized,placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis[J].Hepatology,2018,67(5):1754-1767.
[16]KOLATTUKUDY PE,NIU J.Inflammation,endoplasmic reticulum stress,autophagy,and the monocyte chemoattractant protein-1/CCR2 pathway[J].Circ Res,2012,110(1):174.
[17]KIM HM,LEE ES,LEE BR,et al.C-C chemokine receptor 2inhibitor ameliorates hepatic steatosis by improving ER stress and inflammation in a Type 2 diabetic mouse model[J].PLo SOne,2015,10(3):e0120711.
[18]GEORGI K,ERWIN G,CHRISTOPH D,et al.Hepatic steatosis causes induction of the chemokine RANTES in the absence of significant hepatic inflammation[J].Int J Clin Exp Pathol,2010,3(7):675-680.
[19]KIM BM,ABDELFATTAH AM,VASAN R,et al.Hepatic stellate cells secrete Ccl5 to induce hepatocyte steatosis[J].Sci Rep,2018,8(1):7499.
[20]WU S,YANO S,HISANAGA A,et al.Polyphenols from Lonicera caerulea L.berry attenuate experimental nonalcoholic steatohepatitis by inhibiting proinflammatory cytokines productions and lipid peroxidation[J].Mol Nutr Food Res,2017,61(4):1600858.
[21]KITADE H,SAWAMOTO K,NAGASHIMADA M,et al.CCR5plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status[J].Diabetes,2012,61(7):1680-1690.
[22]HU Y,ZHANG H,LI J,et al.Gut-derived lymphocyte recruitment to liver and induce liver injury in non-alcoholic fatty liver disease mouse model[J].J Gastroenterol Hepatol,2016,31(3):676-684.
[23]CASTRO CA,DA SILVA KA,BUFFO MM,et al.Experimental type 2 diabetes induction reduces serum vaspin,but not serum omentin,in Wistar rats[J].Int J Exp Pathol,2017,98(1):26-33.
[24]BAHCECIOGLU IH,YALNIZ M,ATASEVEN H,et al.Levels of serum hyaluronic acid,TNF-alpha and IL-8 in patients with nonalcoholic steatohepatitis[J].Hepatogastroenterology,2005,52(65):1549-1553.
[25]RUSSO RC,GARCIA CC,TEIXEIRA MM,et al.The CXCL8/IL-8chemokine family and its receptors in inflammatory diseases[J].Expert Rev Clin Immunol,2014,10(5):593-619.
[26]CHAVEZ-TAPIA NC,TIRIBELLI C,ROSSO N.Effect of intracellular lipid accumulation in a new model of non-alcoholic fatty liver disease[J].BMC Gastroenterol,2012,12(1):20.
[27]CENGIZ M,YAASAR DG,ERGUN MA,et al.The role of interleukin-6 and interleukin-8 gene polymorphisms in non-alcoholic steatohepatitis[J].Hepat Mon,2014,14(12):e24635.
[28]GLASS O,HENAO R,PATEL K,et al.Serum interleukin-8,osteopontin,and monocyte chemoattractant protein 1 are associated with hepatic fibrosis in patients with nonalcoholic fatty liver disease[J].Hepatol Commun,2018,2(11):1344-1355.
[29]YIN Z,HUANG J,MA T,et al.Macrophages activating chemokine(C-X-C motif)ligand 8/miR-17 cluster modulate hepatocellular carcinoma cell growth and metastasis[J].Am JTransl Res,2017,9(5):2403.
[30]ZHANG X,HAN J,MAN K,et al.CXC chemokine receptor 3promotes steatohepatitis in mice through mediating inflammatory cytokines,macrophages and autophagy[J].J Hepatol,2016,64(1):160-170.
[31]ZHANG X,SHEN J,MAN K,et al.CXCL10 plays a key role as an inflammatory mediator and a non-invasive biomarker of non-alcoholic steatohepatitis[J].J Hepatol,2014,61(6):1365-1375.
[32]ZHANG X,WU WK,XU W,et al.C-X-C motif chemokine 10impairs autophagy and autolysosome formation in non-alcoholic steatohepatitis[J].Theranostics,2017,7(11):2822-2836.
[33]JINGHUA D,XIANG Z,JUQIANNG H,et al.Pro-inflammatory CXCR3 impairs mitochondrial function in experimental non-alcoholic steatohepatitis[J].Theranostics,2017,7(17):4192-4203.
[34]ZEREMSKI M,PETROVIC LM,CHIRIBOGA L,et al.Intrahepatic levels of cxcr3-associated chemokines correlate with liver inflammation and fibrosis in chronic hepatitis C[J].Hepatology,2008,48(5):1440-1450.
[35]WADA N,TAKAKI A,IKEDA F,et al.Serum-inducible protein(IP)-10 is a disease progression-related marker for non-alcoholic fatty liver disease[J].Hepatol Int,2017,11(1):115-124.
[36]WOLFS MG,GRUBEN N,RENSEN SS,et al.Determining the association between adipokine expression in multiple tissues and phenotypic features of non-alcoholic fatty liver disease in obesity[J].Nutr Diabetes,2015,5(2):e146.
[37]TOMITA K,NIIBE A,FRREEMAN BL,et al.Mixed lineage kinase 3 mediates the induction of CXCL10 by a STAT1-dependent mechanism during hepatocyte lipotoxicity[J].J Cell Biochem,2017,118(10):3249-3259.
[38]TOMITA K,KOHLI R,MACLAURIN BL,et al.Mixed-lineage kinase 3 pharmacological inhibition attenuates murine nonalcoholic steatohepatitis[J].JCI Insight,2017,2(15).pii:94488.
[2]WASMUTH HE,TACKE F,TRAUTWEIN C.Chemokines in liver inflammation and fibrosis[J].Semin Liver Dis,2010,30(3):215-225.
[3]FAHEY S,DEMPSEY E,LONG A.The role of chemokines in acute and chronic hepatitis C infection[J].Cell Mol Immunol,2014,11(1):25-40.
[4]MARRA F,TACKE F.Roles for chemokines in liver disease[J].Gastroenterology,2014,147(3):577-594.e1.
[5]EHOLING J,TACKE F.Role of chemokine pathways in hepatobiliary cancer[J].Cancer Lett,2016,379(2):173-183.
[6]EGAN CE,DAUGHERITY EK,ROGERS AB,et al.CCR2 and CD44 promote inflammatory cell recruitment during fatty liver formation in a lithogenic diet fed mouse model[J].PLo S One,2013,8(6):e65247.
[7]KIROVSKI G,DORN C,HUBER H,et al.Elevated systemic monocyte chemoattractrant protein-1 in hepatic steatosis without significant hepatic inflammation[J].Exp Mol Pathol,2011,91(3):780-783.
[8]SIERRA-FILARDI E,NIETO C,DOMNGUEZ-SOTO A,et al.CCL2 shapes macrophage polarization by GM-CSF and M-CSF:Identification of CCL2/CCR2-dependent gene expression profile[J].Immunol,2014,192(8):3858-3867.
[9]BAECK C,WEI X,BARTNECK M,et al.Pharmacological inhibition of the chemokine C-C motif chemokine ligand 2(monocyte chemoattractant protein 1)accelerates liver fibrosis regression by suppressing Ly-6C(+)macrophage infiltration in mice[J].Hepatology,2014,59(3):1060-1072.
[10]MIURA K,YANG L,van ROOIJEN N,et al.Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through CCR2[J].Am J Physiol Gastrointest Liver Physiol,2012,302(11):g1310-g1321.
[11]CRANFORD TL,ENOS RT,VELAZQUEZ KT,et al.Role of MCP-1 on inflammatory processes and metabolic dysfunction following high-fat feedings in the FVB/N strain[J].Int JObes(Lond),2015,40(5):844-851.
[12]NIO Y,YAMAUCHI T,IWABU M,et al.Monocyte chemoattractant protein-1(MCP-1)deficiency enhances alternatively activated M2 macrophages and ameliorates insulin resistance and fatty liver in lipoatrophic diabetic A-ZIP transgenic mice[J].Diabetologia,2012,55(12):3350-3358.
[13]RICHARD P,WESTON CJ,ZHENHUA M,et al.CC chemokine receptor 2 promotes recruitment of myeloid cells associated with insulin resistance in nonalcoholic fatty liver disease[J].Am J Physiol Gastrointest Liver Physiol,2018,314(4):g483-g493.
[14]ERIC L,GRAEME M,RAN R,et al.Antifibrotic effects of the dual CCR2/CCR5 antagonist cenicriviroc in animal models of liver and kidney fibrosis[J].PLo S One,2016,11(6):e0158156.
[15]FRIEDMAN SL,RATZIU V,HARRISON SA,et al.A randomized,placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis[J].Hepatology,2018,67(5):1754-1767.
[16]KOLATTUKUDY PE,NIU J.Inflammation,endoplasmic reticulum stress,autophagy,and the monocyte chemoattractant protein-1/CCR2 pathway[J].Circ Res,2012,110(1):174.
[17]KIM HM,LEE ES,LEE BR,et al.C-C chemokine receptor 2inhibitor ameliorates hepatic steatosis by improving ER stress and inflammation in a Type 2 diabetic mouse model[J].PLo SOne,2015,10(3):e0120711.
[18]GEORGI K,ERWIN G,CHRISTOPH D,et al.Hepatic steatosis causes induction of the chemokine RANTES in the absence of significant hepatic inflammation[J].Int J Clin Exp Pathol,2010,3(7):675-680.
[19]KIM BM,ABDELFATTAH AM,VASAN R,et al.Hepatic stellate cells secrete Ccl5 to induce hepatocyte steatosis[J].Sci Rep,2018,8(1):7499.
[20]WU S,YANO S,HISANAGA A,et al.Polyphenols from Lonicera caerulea L.berry attenuate experimental nonalcoholic steatohepatitis by inhibiting proinflammatory cytokines productions and lipid peroxidation[J].Mol Nutr Food Res,2017,61(4):1600858.
[21]KITADE H,SAWAMOTO K,NAGASHIMADA M,et al.CCR5plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status[J].Diabetes,2012,61(7):1680-1690.
[22]HU Y,ZHANG H,LI J,et al.Gut-derived lymphocyte recruitment to liver and induce liver injury in non-alcoholic fatty liver disease mouse model[J].J Gastroenterol Hepatol,2016,31(3):676-684.
[23]CASTRO CA,DA SILVA KA,BUFFO MM,et al.Experimental type 2 diabetes induction reduces serum vaspin,but not serum omentin,in Wistar rats[J].Int J Exp Pathol,2017,98(1):26-33.
[24]BAHCECIOGLU IH,YALNIZ M,ATASEVEN H,et al.Levels of serum hyaluronic acid,TNF-alpha and IL-8 in patients with nonalcoholic steatohepatitis[J].Hepatogastroenterology,2005,52(65):1549-1553.
[25]RUSSO RC,GARCIA CC,TEIXEIRA MM,et al.The CXCL8/IL-8chemokine family and its receptors in inflammatory diseases[J].Expert Rev Clin Immunol,2014,10(5):593-619.
[26]CHAVEZ-TAPIA NC,TIRIBELLI C,ROSSO N.Effect of intracellular lipid accumulation in a new model of non-alcoholic fatty liver disease[J].BMC Gastroenterol,2012,12(1):20.
[27]CENGIZ M,YAASAR DG,ERGUN MA,et al.The role of interleukin-6 and interleukin-8 gene polymorphisms in non-alcoholic steatohepatitis[J].Hepat Mon,2014,14(12):e24635.
[28]GLASS O,HENAO R,PATEL K,et al.Serum interleukin-8,osteopontin,and monocyte chemoattractant protein 1 are associated with hepatic fibrosis in patients with nonalcoholic fatty liver disease[J].Hepatol Commun,2018,2(11):1344-1355.
[29]YIN Z,HUANG J,MA T,et al.Macrophages activating chemokine(C-X-C motif)ligand 8/miR-17 cluster modulate hepatocellular carcinoma cell growth and metastasis[J].Am JTransl Res,2017,9(5):2403.
[30]ZHANG X,HAN J,MAN K,et al.CXC chemokine receptor 3promotes steatohepatitis in mice through mediating inflammatory cytokines,macrophages and autophagy[J].J Hepatol,2016,64(1):160-170.
[31]ZHANG X,SHEN J,MAN K,et al.CXCL10 plays a key role as an inflammatory mediator and a non-invasive biomarker of non-alcoholic steatohepatitis[J].J Hepatol,2014,61(6):1365-1375.
[32]ZHANG X,WU WK,XU W,et al.C-X-C motif chemokine 10impairs autophagy and autolysosome formation in non-alcoholic steatohepatitis[J].Theranostics,2017,7(11):2822-2836.
[33]JINGHUA D,XIANG Z,JUQIANNG H,et al.Pro-inflammatory CXCR3 impairs mitochondrial function in experimental non-alcoholic steatohepatitis[J].Theranostics,2017,7(17):4192-4203.
[34]ZEREMSKI M,PETROVIC LM,CHIRIBOGA L,et al.Intrahepatic levels of cxcr3-associated chemokines correlate with liver inflammation and fibrosis in chronic hepatitis C[J].Hepatology,2008,48(5):1440-1450.
[35]WADA N,TAKAKI A,IKEDA F,et al.Serum-inducible protein(IP)-10 is a disease progression-related marker for non-alcoholic fatty liver disease[J].Hepatol Int,2017,11(1):115-124.
[36]WOLFS MG,GRUBEN N,RENSEN SS,et al.Determining the association between adipokine expression in multiple tissues and phenotypic features of non-alcoholic fatty liver disease in obesity[J].Nutr Diabetes,2015,5(2):e146.
[37]TOMITA K,NIIBE A,FRREEMAN BL,et al.Mixed lineage kinase 3 mediates the induction of CXCL10 by a STAT1-dependent mechanism during hepatocyte lipotoxicity[J].J Cell Biochem,2017,118(10):3249-3259.
[38]TOMITA K,KOHLI R,MACLAURIN BL,et al.Mixed-lineage kinase 3 pharmacological inhibition attenuates murine nonalcoholic steatohepatitis[J].JCI Insight,2017,2(15).pii:94488.