PDF下载 ( 2294 KB)
Research advances in cytokines associated with primary biliary cholangitis
-
摘要:
原发性胆汁性胆管炎（PBC）是一种以肝内中小胆管非化脓性炎症为特征的自身免疫性肝病,发病机制尚不明确,免疫调节在其中起关键作用。细胞因子作为免疫系统的重要成分参与其发病。现将近年来研究发现的与PBC有关的一些促炎细胞因子IL-12、IL-17、IL-9、IL-8、TNFα、IL-6和抗炎细胞因子IL-10及其相关信号通路在PBC中的作用作一综述,以加深对PBC发病机制的认识,进而寻求新的治疗方法。
Abstract:Primary biliary cholangitis( PBC) is an autoimmune liver disease characterized by nonsuppurative inflammation of the small-and medium-sized bile ducts in the liver. The pathogenesis of PBC remains unclear,and immunoregulation may play a critical role. As the important components of the immune system,cytokines may be involved in the pathogenesis of PBC. This article reviews related research advances in recent years,including the roles of pro-inflammatory cytokines( interleukin-12,interleukin-17,interleukin-9,interleukin-8,tumor necrosis factor-α,and interleukin-6),the anti-inflammatory cytokine interleukin-10,and their signaling pathways in PBC,so as to deepen the understanding of the pathogenesis of PBC and explore new treatment methods.
-
Key words:
- primary biliary cholangitis /
- cytokines /
- signal transduction
-
[1] TANAKA A,LEUNG PSC,GERSHWIN ME. Evolution of our understanding of PBC[J]. Best Pract Res Clin Gastroenterol,2018,34-35:3-9. [2] GULAMHUSEIN AF,HIRSCHFIELD GM. Pathophysiology of primary biliary cholangitis[J]. Best Pract Res Clin Gastroenterol,2018,34-35:17-25. [3] BANALES JM,SÁEZ E,URIZ M,et al. Up-regulation of microRNA 506 leads to decreased Cl-/HCO3-anion exchanger2 expression in biliary epithelium of patients with primary biliary cirrhosis[J]. Hepatology,2012,56(2):687-697. [4] MA WT,CHEN DK. Immunological abnormalities in patients with primary biliary cholangitis[J]. Clin Sci(Lond),2019,133(6):741-760. [5] WEBB GJ,SIMINOVITCH KA,HIRSCHFIELD GM. The immunogenetics of primary biliary cirrhosis:A comprehensive review[J]. J Autoimmun,2015,64:42-52. [6] GULAMHUSEIN AF,JURAN BD,LAZARIDIS KN. Genomewide association studies in primary biliary cirrhosis[J]. Semin Liver Dis,2015,35(4):392-401. [7] YOSHIDA K,YANG GX,ZHANG W,et al. Deletion of interleukin-12p40 suppresses autoimmune cholangitis in dominant negative transforming growth factor beta receptor type II mice[J]. Hepatology,2009,50(5):1494-1500. [8] LAN RY,SALUNGA TL,TSUNEYAMA K,et al. Hepatic IL-17 responses in human and murine primary biliary cirrhosis[J]. J Autoimmun,2009,32(1):43-51. [9] YANG W,YAO Y,YANG YQ,et al. Differential modulation by IL-17A of cholangitis versus colitis in IL-2Rαdeleted mice[J]. PLo S One,2014,9(8):e105351. [10] KAWATA K,TSUDA M,YANG GX,et al. Identification of potential cytokine pathways for therapeutic intervention in murine primary biliary cirrhosis[J]. PLo S One,2013,8(9):e74225. [11] SHI T,ZHANG T,ZHANG L,et al. The distribution and the fibrotic role of elevated inflammatory Th17 cells in patients with primary biliary cirrhosis[J]. Medicine(Baltimore),2015,94(44):e1888. [12] ZHANG H,BERNUZZI F,LIEO A,et al. Therapeutic potential of IL-17-mediated signaling pathway in autoimmune liver diseases[J]. Mediators Inflamm,2015,2015:436450. [13] YANG CY,MA X,TSUNEYAMA K,et al. IL-12/Th1 and IL-23/Th17 biliary microenvironment in primary biliary cirrhosis:Implications for therapy[J]. Hepatology,2014,59(5):1944-1953. [14] ELYAMAN W,BRADSHAW EM,UYTTENHOVE C,et al. IL-9induces differentiation of Th17 cells and enhances function of Fox P3+natural regulatory T cells[J]. Proc Natl Acad Sci U S A,2009,106(31):12885-12890. [15] XIAO X,BIAN ZL,MIAO Q,et al. Expression and clinical significance of interleukin-9 in patients with primary biliary cirrhosis[J]. Chin J Gastroenter,2014,19(8):464-467.(in Chinese)肖潇，卞兆连，苗琪，等．白细胞介素-9在原发性胆汁性肝硬化患者中的表达及其临床意义[J]．胃肠病学，2014,19(8):464-467. [16] LI H,CHEN Y,ZHANG L,et al. Expression of Th9 cells from peripheral blood of primary biliary cirrhosis patients and its clinical significance[J]. J Mod Lab Med,2016,31(3):16-18,21.(in Chinese)李虎，陈燕，张蕾，等．原发性胆汁性肝硬化患者外周血Th9细胞表达增高及其临床意义[J]．现代检验医学杂志，2016,31(3):16-18,21. [17] WANG Q,LUO DM,SUN XF,et al. Increased expression of IL-9 in peripheral blood and liver tissues of patients with primary biliary cirrhosis[J]. Chin J Cell Mol Immunol,2016,32(12):1679-1682.(in Chinese)王倩，罗德梅，孙晓凤，等．原发性胆汁性肝硬化患者血清和肝组织白细胞介素9表达增强[J]．细胞与分子免疫学杂志，2016,32(12):1679-1682. [18] QIN SY,LU DH,GUO XY,et al. A deleterious role for Th9/IL-9in hepatic fibrogenesis[J]. Sci Rep,2016,6:18694. [19] GUO X,CEN Y,WANG J,et al. CXCL10-induced IL-9promotes liver fibrosis via Raf/MEK/ERK signaling pathway[J]. Biomed Pharmacother,2018,105:282-289. [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-MAPK signaling pathways[J]. Liver Int,2006,26(4):467-476. [22] REN Y,POON RT,TSUI HT,et al. Interleukin-8 serum levels in patients with hepatocellular carcinoma:Correlations with clinicopathological features and prognosis[J]. Clin Cancer Res,2003,9(1):5996-6001. [23] HARADA K,HIROHARA J,UENO Y,et al. Incidence of and risk factors for hepatocellular carcinoma in primary biliary cirrhosis:National data from Japan[J]. Hepatology,2013,57(5):1942-1949. [24] ZIMMERMANN HW,SEIDLER S,GASSLER N,et al. Interleukin-8 is 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. [25] 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. [26] AKBEROVA D,KIASSOV AP,ABDULGANIEVA D. Serum cytokine levels and their relation to clinical features in patients with autoimmune liver diseases[J]. J Immunol Res,2017,2017:9829436. [27] 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. [28] NEUMAN M,ANGULO P,MALKIEWICZ I,et al. Tumor necrosis factor-alpha and transforming growth factor-beta reflect severity of liver damage in primary biliary cirrhosis[J]. J Gastroenterol Hepatol,2002,17(2):196-202. [29] ZHANG W,TSUDA M,YANG GX,et al. Deletion of interleukin-6in mice with the dominant negative form of transforming growth factor beta receptor II improves colitis but exacerbates autoimmune cholangitis[J]. Hepatology,2010,52(1):215-222. [30] SPADARO A,SCRIVO R,RICCIERI V,et al. Effect of tumor necrosis factor alpha antagonists in a patient with rheumatoid arthritis and primary biliary cirrhosis[J]. Joint Bone Spine,2008,75(1):87-89. [31] TRIANTAFILLIDIS JK,DURAKIS S,MERIKAS E. Crohn’s disease of the small bowel,complicated by primary biliary cirrhosis,Hashimoto thyroiditis,and Raynaud’s phenomenon:Favorable response of all disorders to adalimumab treatment[J].Gastroenterol Hepatol Bed Bench,2013,6(2):101-105. [32] DEL ROSS T,RUFFATTI A,FLOREANI A,et al. The efficacy of adalimumab in psoriatic arthritis concomitant to overlapping primary biliary cholangitis and primary sclerosing cholangitis:A case report[J]. BMC Musculoskelet Disord,2016,17(1):485. [33] CHEN LP,CAI M,ZHANG QH,et al. Activation of interleukin-6/STAT3 in rat cholangiocyte proliferation induced by lipopolysaccharide[J]. Dig Dis Sci,2009,54(3):547-554. [34] SAITO E,SATO S,NOGI S,et al. A case of rheumatoid arthritis and limited systemic sclerosis overlap successfully treated with tocilizumab for arthritis and concomitant generalized lymphadenopathy and primary biliary cirrhosis[J]. Case Rep Rheumatol,2014,2014:386328. [35] CHEN J,HOU X,JIA H,et al. Regulatory T cells with a defect in inhibition on co-stimulation deteriorated primary biliary cholangitis[J]. Oncotarget,2017,8(65):108406-108417. [36] LIASKOU E,PATEL SR,WEBB G,et al. Increased sensitivity of Treg cells from patients with PBC to low dose IL-12 drives their differentiation into IFN-gamma secreting cells[J]. J Autoimmun,2018,94:143-155. [37] ZHANG W,SHARMA R,JU ST,et al. Deficiency in regulatory T cells results in development of antimitochondrial antibodies and autoimmune cholangitis[J]. Hepatology,2009,49(2):545-552. [38] TANAKA H,ZHANG W,YANG GX,et al. Successful immunotherapy of autoimmune cholangitis by adoptive transfer of forkhead box protein 3(+)regulatory T cells[J]. Clin Exp Immunol,2014,178(2):253-261. [39] WANG L,HAN Y. An excerpt of primary biliary cholangitis:2018practice guidance from the American Association for the Study of Liver Diseases[J]. J Clin Hepatol,2018,34(11):2300-2304.(in Chinese)王璐，韩英．《2018年美国肝病学会原发性胆汁性胆管炎实践指导》摘译[J]．临床肝胆病杂志，2018,34(11):2300-2304. [40] HIRSCHFIELD GM,GERSHWIN ME,STRAUSS R,et al. Ustekinumab for patients with primary biliary cholangitis who have an inadequate response to ursodeoxycholic acid:A proof-of-concept study[J]. Hepatology,2016,64(1):189-199. [41] TODO S,YAMASHITA K,GOTO R,et al. A pilot study of operational tolerance with a regulatory T-cell-based cell therapy in living donor liver transplantation[J]. Hepatology,2016,64(2):632-643. [42] POPP F,SEMELA D,von KEMPIS J,et al. Improvement of primary biliary cholangitis(PBC)under treatment with sulfasalazine and abatacept[J]. BMJ Case Rep,2018,2018:bcr-2018-224205. [43] BOWLUS CL,YANG GX,LIU CH,et al. Therapeutic trials of biologics in primary biliary cholangitis:An open label study of abatacept and review of the literature[J]. J Autoimmun,2019,101:26-34. [44] KISHIDA K,KOHYAMA M,KURASHIMA Y,et al. Negative regulation of DSS-induced experimental colitis by PILRalpha[J]. Int Immunol,2015,27(6):307-314. -
本文二维码
计量
- 文章访问数: 825
- HTML全文浏览量: 44
- PDF下载量: 245
- 被引次数: 0
下载:
