Kupffer cell function in liver fibrosis and fibrolysis: A double-edged sword?
-
摘要: 肝脏纤维化的发生机制尚不完全明确,研究发现肝内巨噬细胞(Kupffer细胞)在肝纤维化发生发展过程中发挥重要作用。Kupffer细胞主要通过受体介导及细胞因子表达和分型变化影响纤维化形成;分泌促纤维化的转化生长因子(TGF)β1和血小板衍生生长因子(PDGF),或促纤维降解的基质金属蛋白酶-13等,导致Kupffer细胞在不同纤维化阶段发挥不同的调节肝纤维化的作用,本文综述Kupffer细胞在肝纤维化发生过程中双向调节作用,以期为肝纤维化的研究提供新的临床思路。Abstract: The underlying mechanisms of liver fibrosis have not yet been fully elucidated.Studies with models of toxic or cholestatic liver fibrosis have implicated Kupffer cells, the largest group of resident liver macrophages, as playing a critical role in the pathogenic process.Kupffer cell receptor activation, cytokine expression, and phenotype may contribute to the onset or progression of liver fibrosis.Pro-fibrotic cytokines, such as transforming growth factor β1, platelet-derived growth factor and anti-fibrotic matrix metalloproteinase 13, are known to play a pivotal role in both fibrogenesis and fibrolysis.In this review, we discuss the known functions and dynamic molecular processes of Kupffer cells during liver fibrosis to provide further insights into the underlying pathogenic mechanisms of this disease.
-
Key words:
- liver cirrhosis /
- kupffer cell
-
[1]Gao B, Jeong WI, Tian Z.Liver:An organ with predominantinnate immunity[J].Hepatology, 2008, 47 (2) :729-736. [2]龚建平, 廖汪洋, 何益平, 等.Kupffer细胞与HBV慢性感染引起的肝损伤[J].世界华人消化杂志, 2008, 16 (24) :2735-2740. [3]邢汉前, 辛绍杰, 赵景民, 等.HBV慢性感染免疫耐受期患者肝组织内NK细胞及Kupffer细胞的研究[J].中国现代医学杂志, 2007, 17 (11) :1330-1333. [4]刘伟, 赵伟, 罗婵, 等.乙型肝炎患者血清HBV DNA负荷和肝组织超微结构损伤的相关性[J].临床肝胆病杂志, 2005, 21 (6) :329-330. [5]Reinke P, David H, Uerlings I, et al.Electron microscopy ofliver in patients with chronic haemodialysis[J].Exp Pathol, 1991, 42 (2) :65-75. [6]Vollmar B, Siegmund S, Richter S, et al.Microvascular con-sequences of Kupffer cell modulation in rat liver fibrogenesis[J].J Pathol, 1999, 189 (1) :85-91. [7]Kolios G, Valatas V, Kouroumalis E.Role of Kupffer cells inthe pathogenesis of liver disease[J].World J Gastroenterol, 2006, 12 (46) :7413-7420. [8]Chin D, Boyle GM, Parsons PG, et al.What is transforminggrowth factor-beta (TGF-beta) ?[J].Br J Plast Surg, 2004, 57 (3) :215-221. [9]Nieto N.Oxidative-stress and IL-6 mediate the fibrogeniceffects of Kupffer cells on stellate cells[J].Hepatology, 2006, 44 (6) :1487-1501. [10]Wynn TA, Barron L.Macrophages:master regulators of in-flammation and fibrosis[J].Semin Liver Dis, 2010, 30 (3) :245-257. [11]Muriel P, Escobar Y.Kupffer cells are responsible for livercirrhosis induced by carbon tetrachloride[J].J Appl Toxicol, 2003, 23 (2) :103-108. [12]Duffield JS, Forbes SJ, Constandinou CM, et al.Selectivedepletion of macrophages reveals distinct, opposing rolesduring liver injury and repair[J].J Clin Invest, 2005, 115 (1) :56-65. [13]Friedman SL.Mac the knife?Macrophages-the double-edged sword of hepatic fibrosis[J].J Clin Invest, 2005, 115 (1) :29-32. [14]Liu C, Tao Q, Sun M, et al.Kupffer cells are associated withapoptosis, inflammation and fibrotic effects in hepatic fibrosis inrats[J].Lab Invest, 2010, 90 (12) :1805-1816. [15]Popov Y, Sverdlov DY, Bhaskar KR, et al.Macrophage-medi-ated phagocytosis of apoptotic cholangiocytes contributes to re-versal of experimental biliary fibrosis[J].Am J Physiol Gastroi-ntest Liver Physiol, 2010, 298 (3) :G323-334. [16]Tacke F, Luedde T, Trautwein C.Inflammatory pathways inliver homeostasis and liver injury[J].Clin Rev Allergy Immu-nol, 2009, 36 (1) :4-12. [17]Wickert L, Abiaka M, Bolkenius U, et al.Corticosteroids stimu-late selectively transforming growth factor (TGF) -beta recep-tor type III expression in transdifferentiating hepatic stellate cells[J].J Hepatol, 2004, 40 (1) :69-76. [18]Poli G.Pathogenesis of liver fibrosis:role of oxidative stress[J].Mol Aspects Med, 2000, 21 (3) :49-98. [19]Higuchi H, Gores GJ.Mechanisms of liver injury:an over-view[J].Curr Mol Med, 2003, 3 (6) :483-490. [20]Mosser DM, Edwards JP.Exploring the full spectrum of macro-phage activation[J].Nat Rev Immunol, 2008, 8 (12) :958-969. [21]Karlmark KR, Weiskirchen R, Zimmermann HW, et al.He-patic recruitment of the inflammatory Gr1 (+) monocytesubset upon liver injury promotes hepatic fibrosis[J].Hepa-tology, 2009, 50 (1) :261-274. [22]Stout RD, Jiang C, Matta B, et al.Macrophages sequential-ly change their functional phenotype in response to changesin microenvironmental influences[J].J Immunol, 2005, 175 (1) :342-349. [23]Arthur MJ.Degradation of matrix proteins in liver fibrosis[J].Pathol Res Pract, 1994, 190 (9-10) :825-833. [24]Morris SM Jr.Arginine:master and commander in innate im-mune responses[J].Sci Signal, 2010, 3 (135) :pe27. [25]Wahl SM, Hunt DA, Wong HL, et al.Transforming growthfactor-beta is a potent immunosuppressive agent that inhib-its IL-1-dependent lymphocyte proliferation[J].J Immu-nol, 1988, 140 (9) :3026-3032. [26]Lebman DA, Edmiston JS.The role of TGF-beta in growth, differentiation, and maturation of B lymphocytes[J].Mi-crobes Infect, 1999, 1 (15) :1297-1304. [27]Harris J, De Haro SA, Master SS, et al.T helper 2 cytokinesinhibit autophagic control of intracellular Mycobacterium tu-berculosis[J].Immunity, 2007, 27 (3) :505-517. [28]Muller U, Stenzel W, Kohler G, et al.IL-13 induces dis-ease-promoting type 2 cytokines, alternatively activatedmacrophages and allergic inflammation during pulmonary in-fection of mice with Cryptococcus neoformans[J].J Immu-nol, 2007, 179 (8) :5367-5377. [29]Tumitan AR, Monnazzi LG, Ghiraldi FR, et al.Pattern of macro-phage activation in yersinia-resistant and yersinia-susceptiblestrains of mice[J].Microbiol Immunol, 2007, 51 (10) :1021-1028. [30]Shirey KA, Cole LE, Keegan AD, et al.Francisella tularensislive vaccine strain induces macrophage alternative activationas a survival mechanism[J].J Immunol, 2008, 181 (6) :4159-4167. [31]Li H, Zheng HW, Chen H, et al.Hepatitis B virus particlespreferably induce Kupffer cells to produce TGF-beta1 overpro-inflammatory cytokines[J].Dig Liver Dis, 2012, 44 (4) :328-333. [32]Miles SA, Conrad SM, Alves RG, et al.A role for IgG im-mune complexes during infection with the intracellular patho-gen Leishmania[J].J Exp Med, 2005, 201 (5) :747-754. [33]Villalta SA, Rinaldi C, Deng B, et al.Interleukin-10 reducesthe pathology of mdx muscular dystrophy by deactivating M1macrophages and modulating macrophage phenotype[J].Hum Mol Genet, 2011, 20 (4) :790-805. [34]Benoit M, Barbarat B, Bernard A, et al.Coxiella burnetii, the agent of Q fever, stimulates an atypical M2 activationprogram in human macrophages[J].Eur J Immunol, 2008, 38 (4) :1065-1070. [35]李海.免疫细胞对肝脏纤维化的调控作用[J].临床肝胆病杂志, 2012, 28 (1) :74-77.
本文二维码
计量
- 文章访问数: 3665
- HTML全文浏览量: 27
- PDF下载量: 830
- 被引次数: 0