趋化因子与肝病的研究进展
胡迎宾,田德安, 刘南植,华中科技大学同济医学院附属同济医院消化内科 湖北省武汉市 430030
项目负责人: 田德安,430030,湖北省武汉市航空路13号,华中科技大学同济医学院附属同济医院消化内科. tiandeanwh@sina.com
电话:027-83643609 传真:027-83643609
收稿日期:2002-11-12 接受日期:2002-11-29
摘要近年来，趋化因子(Chemokines)在肝病发病机制中的作用越来越受到重视.大量研究表明，趋化因子在各种肝损伤中表达上调.通过应用趋化因子抑制剂，特异性趋化因子缺陷动物模型以及调控趋化因子受体等方法，趋化因子与炎症细胞浸润的密切关系得以证实.而在肝脏慢性炎症中，炎症因子、生长因子、氧应激及其产物等刺激因素促进趋化因子的表达.高表达的趋化因子能激活肝星状细胞(HSC)参与肝纤维化甚至肝硬化的形成.由于趋化因子有促进血管生成和新生物增生的作用，其与肿瘤的关系也成为研究的热点.本文将阐述趋化因子在酒精性肝病，肝纤维化，肝硬化和肝癌中的作用机制.
, 百拇医药
胡迎宾, 田德安,刘南植. 趋化因子与肝病的研究进展. 世界华人消化杂志 2003;11(7):1040-1042
Sheron N, Bird G, Koskinas J, Portmann B, Ceska M, Lindley I,Williams R. Circulating and tissue levels of the
neutrophil chemotaxin interleukin-8 areelevated in severe acute alcoholic hepatitis, and tissue levelscorrelate
with neutrophil infiltration. Hepatology 1993; 18:41 -46
2 Hill DB, Marsano LS, McClain CJ. Increased plasma interleukin-8concentrations in alcoholic hepatitis. Hepatology
, 百拇医药
1993;18:576-580
3 Huang YS, Chan CY, Wu JC, Pai CH, Chao Y, Lee SD. Serum levels ofinterleukin-8 in alcoholic liver disease:
relationship with disease stage,biochemical parameters and survival. J Hepatol 1996;24:377-384
4 Shiratori Y, Takada H, Hikiba Y, Nakata R, Okano K, Komatsu Y, NiwaY, Matsumura M, Shiina S, Omata M, Kamii
K. Production of chemotactic factor,interleukin-8, from hepatocytes exposed to ethanol. Hepatology
, http://www.100md.com
1993;18:1477-1482
5 Nanji AA, Jokelainen K, Rahemtulla A, Miao L, Fogt F, Matsumoto H,Tahan SR, Su GL. Activation of nuclear factor kappa
B and cytokine imbalance in experimentalalcoholic liver disease in the rat. Hepatology 1999; 30:934-943
6 Kharbanda KK, Todero SL, Shubert KA, Sorrell MF, Tuma DJ.Malondialdehyde-acetaldehyde protein adducts
increase secretion of chemokines by rathepatic stellate cells. Alcohol 2001;25:123-128
, 百拇医药
7 Afford SC, Fisher NC, Neil DA, Fear J, Brun P, Hubscher SG, AdamsDH. Distinct patterns of chemokine expression
are associated with leukocyte recruitmentin alcoholic hepatitis and alcoholic cirrhosis. J Pathol 1998;186:82-89
8 Maher JJ, Scott MK, Saito JM, Burton MC. Adenovirus-mediatedexpression of cytokine-induced neutrophil
chemoattractant in rat liver induces aneutrophilic hepatitis. Hepatology 1997;25:624-630
, 百拇医药
9 Maltby J, Wright S, Bird G, Sheron N. Chemokine levels in humanliver homogenates: associations between GRO alpha
and histopathological evidence of alcoholichepatitis. Hepatology 1996;24:1156-1160
10 Fisher NC, Neil DA, Williams A,Adams DH. Serum concentrations and peripheral secretion of the beta chemokines
monocytechemoattractant protein 1 and macrophage inflammatory protein 1 alpha inalcoholic liver disease.
, http://www.100md.com
Gut 1999;45:416-420
11 Zhang P, Bagby GJ, Boe DM, Zhong Q, Schwarzenberger P, Kolls JK,Summer WR, Nelson S. Acute alcohol
intoxication suppresses the CXC chemokineresponse during endotoxemia. Alcohol Clin Exp Res 2002;26:65-73
12 Sprenger H, Kaufmann A, Garn H, Lahme B, Gemsa D, Gressner AM.Differential expression of monocyte
chemotactic protein-1 (MCP-1) intransforming rat hepatic stellate cells. J Hepatol 1999;30:88-94
, 百拇医药
13 Marra F, Pastacaldi S, Romanelli RG, Pinzani M, Ticali P, CarloniV, Laffi G, Gentilini P. Integrin-mediated stimulation
of monocyte chemotactic protein-1expression. FEBS Lett 1997;414:221-225
14 Czaja MJ, Geerts A, Xu J, Schmiedeberg P, Ju Y. Monocytechemoattractant protein 1 (MCP-1) expression occurs in
toxic rat liver injury and human liverdisease. J Leukoc Biol 1994;55:120-126
, 百拇医药
15 Marra F, DeFranco R, Grappone C, Milani S, Pastacaldi S, Pinzani M,Romanelli RG, Laffi G, Gentilini P.
Increased expression of monocytechemotactic protein-1 during active hepatic fibrogenesis: correlationwith
monocyte infiltration. Am J Pathol 1988;152:423-430
16 Sprenger H, Kaufmann A, Garn H, Lahme B, Gemsa D, Gressner AM.Induction of neutrophil-attracting chemokines
, http://www.100md.com
in transforming rat hepatic stellate cells.Gastroenterology 1997;113:277-285
17 Maher JJ, Lozier JS, Scott MK. Rat hepatic stellate cells producecytokine-induced neutrophil chemoattractant in culture
and in vivo. Am J Physiol 1998;275:G847-G853
18 Marra F, Efsen E, Romanelli RG, Caligiuri A, Pastacaldi S,Batignani G, Bonacchi A, Caporale R, Laffi G, Pinzani M,Gentilini P. Ligands of peroxisomeproliferator-activated receptor gamma modulate profibrogenic andproinflammatory
, 百拇医药
actions in hepatic stellate cells.Gastroenterology 2000;119:466-478
19 Schwabe RF, Schnabl B, Kweon YO, Brenner DA. CD40 activatesNF-kappa B and c-Jun N-terminal kinase and
enhances chemokine secretion on activatedhuman hepatic stellate cells. J Immunol 2001;166:6812-6819
20 Bonacchi A, Romagnani P, Romanelli RG, Efsen E, Annunziato F,Lasagni L, Francalanci M, Serio M, Laffi G, Pinzani
M, Gentilini P, Marra F. Signaltransduction by the chemokine receptor CXCR3. Activation of Ras/ERK, Srcand
phosphatidylinositol 3-kinase/Akt controlscell migration and proliferation in human vascular pericytes. J Biol Chem
2001;276:9945-9954, http://www.100md.com( 胡迎宾, 田德安, 刘南植)
项目负责人: 田德安,430030,湖北省武汉市航空路13号,华中科技大学同济医学院附属同济医院消化内科. tiandeanwh@sina.com
电话:027-83643609 传真:027-83643609
收稿日期:2002-11-12 接受日期:2002-11-29
摘要近年来，趋化因子(Chemokines)在肝病发病机制中的作用越来越受到重视.大量研究表明，趋化因子在各种肝损伤中表达上调.通过应用趋化因子抑制剂，特异性趋化因子缺陷动物模型以及调控趋化因子受体等方法，趋化因子与炎症细胞浸润的密切关系得以证实.而在肝脏慢性炎症中，炎症因子、生长因子、氧应激及其产物等刺激因素促进趋化因子的表达.高表达的趋化因子能激活肝星状细胞(HSC)参与肝纤维化甚至肝硬化的形成.由于趋化因子有促进血管生成和新生物增生的作用，其与肿瘤的关系也成为研究的热点.本文将阐述趋化因子在酒精性肝病，肝纤维化，肝硬化和肝癌中的作用机制.
, 百拇医药
胡迎宾, 田德安,刘南植. 趋化因子与肝病的研究进展. 世界华人消化杂志 2003;11(7):1040-1042
Sheron N, Bird G, Koskinas J, Portmann B, Ceska M, Lindley I,Williams R. Circulating and tissue levels of the
neutrophil chemotaxin interleukin-8 areelevated in severe acute alcoholic hepatitis, and tissue levelscorrelate
with neutrophil infiltration. Hepatology 1993; 18:41 -46
2 Hill DB, Marsano LS, McClain CJ. Increased plasma interleukin-8concentrations in alcoholic hepatitis. Hepatology
, 百拇医药
1993;18:576-580
3 Huang YS, Chan CY, Wu JC, Pai CH, Chao Y, Lee SD. Serum levels ofinterleukin-8 in alcoholic liver disease:
relationship with disease stage,biochemical parameters and survival. J Hepatol 1996;24:377-384
4 Shiratori Y, Takada H, Hikiba Y, Nakata R, Okano K, Komatsu Y, NiwaY, Matsumura M, Shiina S, Omata M, Kamii
K. Production of chemotactic factor,interleukin-8, from hepatocytes exposed to ethanol. Hepatology
, http://www.100md.com
1993;18:1477-1482
5 Nanji AA, Jokelainen K, Rahemtulla A, Miao L, Fogt F, Matsumoto H,Tahan SR, Su GL. Activation of nuclear factor kappa
B and cytokine imbalance in experimentalalcoholic liver disease in the rat. Hepatology 1999; 30:934-943
6 Kharbanda KK, Todero SL, Shubert KA, Sorrell MF, Tuma DJ.Malondialdehyde-acetaldehyde protein adducts
increase secretion of chemokines by rathepatic stellate cells. Alcohol 2001;25:123-128
, 百拇医药
7 Afford SC, Fisher NC, Neil DA, Fear J, Brun P, Hubscher SG, AdamsDH. Distinct patterns of chemokine expression
are associated with leukocyte recruitmentin alcoholic hepatitis and alcoholic cirrhosis. J Pathol 1998;186:82-89
8 Maher JJ, Scott MK, Saito JM, Burton MC. Adenovirus-mediatedexpression of cytokine-induced neutrophil
chemoattractant in rat liver induces aneutrophilic hepatitis. Hepatology 1997;25:624-630
, 百拇医药
9 Maltby J, Wright S, Bird G, Sheron N. Chemokine levels in humanliver homogenates: associations between GRO alpha
and histopathological evidence of alcoholichepatitis. Hepatology 1996;24:1156-1160
10 Fisher NC, Neil DA, Williams A,Adams DH. Serum concentrations and peripheral secretion of the beta chemokines
monocytechemoattractant protein 1 and macrophage inflammatory protein 1 alpha inalcoholic liver disease.
, http://www.100md.com
Gut 1999;45:416-420
11 Zhang P, Bagby GJ, Boe DM, Zhong Q, Schwarzenberger P, Kolls JK,Summer WR, Nelson S. Acute alcohol
intoxication suppresses the CXC chemokineresponse during endotoxemia. Alcohol Clin Exp Res 2002;26:65-73
12 Sprenger H, Kaufmann A, Garn H, Lahme B, Gemsa D, Gressner AM.Differential expression of monocyte
chemotactic protein-1 (MCP-1) intransforming rat hepatic stellate cells. J Hepatol 1999;30:88-94
, 百拇医药
13 Marra F, Pastacaldi S, Romanelli RG, Pinzani M, Ticali P, CarloniV, Laffi G, Gentilini P. Integrin-mediated stimulation
of monocyte chemotactic protein-1expression. FEBS Lett 1997;414:221-225
14 Czaja MJ, Geerts A, Xu J, Schmiedeberg P, Ju Y. Monocytechemoattractant protein 1 (MCP-1) expression occurs in
toxic rat liver injury and human liverdisease. J Leukoc Biol 1994;55:120-126
, 百拇医药
15 Marra F, DeFranco R, Grappone C, Milani S, Pastacaldi S, Pinzani M,Romanelli RG, Laffi G, Gentilini P.
Increased expression of monocytechemotactic protein-1 during active hepatic fibrogenesis: correlationwith
monocyte infiltration. Am J Pathol 1988;152:423-430
16 Sprenger H, Kaufmann A, Garn H, Lahme B, Gemsa D, Gressner AM.Induction of neutrophil-attracting chemokines
, http://www.100md.com
in transforming rat hepatic stellate cells.Gastroenterology 1997;113:277-285
17 Maher JJ, Lozier JS, Scott MK. Rat hepatic stellate cells producecytokine-induced neutrophil chemoattractant in culture
and in vivo. Am J Physiol 1998;275:G847-G853
18 Marra F, Efsen E, Romanelli RG, Caligiuri A, Pastacaldi S,Batignani G, Bonacchi A, Caporale R, Laffi G, Pinzani M,Gentilini P. Ligands of peroxisomeproliferator-activated receptor gamma modulate profibrogenic andproinflammatory
, 百拇医药
actions in hepatic stellate cells.Gastroenterology 2000;119:466-478
19 Schwabe RF, Schnabl B, Kweon YO, Brenner DA. CD40 activatesNF-kappa B and c-Jun N-terminal kinase and
enhances chemokine secretion on activatedhuman hepatic stellate cells. J Immunol 2001;166:6812-6819
20 Bonacchi A, Romagnani P, Romanelli RG, Efsen E, Annunziato F,Lasagni L, Francalanci M, Serio M, Laffi G, Pinzani
M, Gentilini P, Marra F. Signaltransduction by the chemokine receptor CXCR3. Activation of Ras/ERK, Srcand
phosphatidylinositol 3-kinase/Akt controlscell migration and proliferation in human vascular pericytes. J Biol Chem
2001;276:9945-9954, http://www.100md.com( 胡迎宾, 田德安, 刘南植)
