[1]熊慧敏,许小凡,段丽芳,等.白细胞介素-6在胰腺炎症和肿瘤中的作用机制研究进展[J].新乡医学院学报,2019,36(12):1191-1196.[doi:10.7683/xxyxyxb.2019.12.022]
点击复制

白细胞介素-6在胰腺炎症和肿瘤中的作用机制研究进展
分享到:

《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
36
期数:
2019年12
页码:
1191-1196
栏目:
综述
出版日期:
2019-12-12

文章信息/Info

作者:
熊慧敏许小凡段丽芳张 红
(陕西中医药大学基础医学院,陕西 西安 712046)
关键词:
白细胞介素-6 Janus激酶/信号传导与转录激活信号胰腺炎胰腺癌
分类号:
R576
DOI:
10.7683/xxyxyxb.2019.12.022
文献标志码:
A
摘要:
白细胞介素-6(IL-6)是一种重要的炎性因子,与胰腺外分泌疾病如急性胰腺炎、慢性胰腺炎和胰腺癌等的发生、发展密切相关。多项研究表明,IL-6主要通过Janus激酶/信号传导与转录激活信号(JAK/STAT)通路的激活,进而促进胰腺炎症及肿瘤的发生和发展。深入研究IL-6及JAK/STAT通路参与急性胰腺炎、慢性胰腺炎及胰腺癌的发生机制将为其治疗提供新思路。本文就IL-6在胰腺炎症和肿瘤中的作用机制相关研究作一综述。

参考文献/References:

[1] LESINA M,WRMANN S M,NEUHFER P,et al.Interleukin-6 in inflammatory and malignant diseases of the pancreas[J].Semin Immunol,2014,26(1):80-87.
[2] KISHIMOTO T.IL-6:from its discovery to clinical applications[J].Int Immunol,2010,22(5):347-352.
[3] KISHIMOTO T,ISHIZAKA K.Regulation of antibody response in vitro.Heavy chain antigenic determinants on hapten-specific memory cell[J].J Immunol,1972,109(6):1163-1173.
[4] ZHANG H,NEUHFER P,SONG L,et al.IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality[J].J Clin Invest,2013,123(3):1019-1031.
[5] WOLVEKAMP M C,MARQUET R L.Interleukin-6:historical background,genetics and biological significance[J].Immunol Lett,1990,24(1):1-9.
[6] ROSE-JOHN S.IL-6 trans-signaling via the soluble IL-6 receptor:importance for the pro-inflammatory activities of IL-6[J].Int J Biol Sci,2012,8(9):1237-1247.
[7] ROBINSON K,VONA-DAVIS L,RIGGS D,et al.Peptide YY attenuates STAT1 and STAT3 activation induced by TNF-α in acinar cell line AR42J[J].J Am Coll Surg,2006,202(5):788-796.
[8] LAVECCHIA A,DI C G,NOVELLINO E.STAT-3 inhibitors:state of the art and new horizons for cancer treatment[J].Curr Med Chem,2011,18(16):2359-2375.
[9] GARBERS C,APARICIO-SIEGMUND S,ROSE-JOHN S.The IL-6/gp130/STAT3 signaling axis:recent advances towards specific inhibition[J].Curr Opin Immunol,2015,34(6):75-82.
[10] CLOSA D,MOTOO Y,IOVANNA J L.Pancreatitis-associated protein:from a lectin to an anti-inflammatory cytokine[J].World J Gastroenterology,2007,13(2):170-174.
[11] BARATTA M G.STAT3′s true colours[J].Nat Rev Cancer,2018,18(11):664-665.
[12] LEE D S,O′KEEFE R A,HA P K,et al.Biochemical properties of a decoy oligodeoxynucleotide inhibitor of STAT3 transcription factor[J].Int J Mol Sci,2018,19(6).pii:E1608.DOI:10.3390/ijms19061608.
[13] TANAKA T,NARAZAKI M,KISHIMOTO T.Anti-interleukin-6 receptor antibody,tocilizumab,for the treatment of autoimmune diseases[J].Febs Lett,2011,585(23):3699-3709.
[14] YU J H,KIM K H,KIM H.SOCS 3 and PPAR-γ ligands inhibit the expression of IL-6 and TGF-β1 by regulating JAK2/STAT3 signaling in pancreas[J].Int J Biochem Cell Biol,2008,40(4):677-688.
[15] PAPACHRISTOU G I.Prediction of severe acute pancreatitis:current knowledge and novel insights[J].World J Gastroenterology,2008,14(41):6273-6275.
[16] BHATIA M.Acute pancreatitis as a model of SIRS[J].Front Biosci,2009,14(14):2042-2050.
[17] SCHUTTE K,MALFERTHEINER P.Markers for predicting severity and progression of acute pancreatitis[J].Best Pract Res Clin Gastroenterol,2008,22(1):75-90.
[18] NOVOVIC S,ANDERSEN A M,ERSBLL A K,et al.Proinflammatory cytokines in alcohol or gallstone induced acute pancreatitis.A prospective study[J].Jop,2009,10(3):256-262.
[19] LEAL C,ALMEIDA N.Predicting severity in acute pancreatitis:a never-ending question[J].Ge Port J Gastroenterol,2019,26(4):232-234.
[20] BA AK F,HASBAHECI M, I IK A,et al.Can C-reactive protein levels increase the accuracy of the Ranson score in predicting the severity and prognosis of acute pancreatitis? A prospective cohort study[J].Turk J Gastroenterol,2017,28(3):207-213.
[21] RAU B,STEINBACH G,BAUMGART K,et al.Serum amyloid A versus C-reactive protein in acute pancreatitis:clinical value of an alternative acute-phase reactant[J].Crit Care Med,2000,28(3):736-742.
[22] GOODCHILD G,CHOUHAN M,JOHNSON G J.Practical guide to the management of acute pancreatitis[J].Frontline Gastroenterol,2019,10(3):292-299.
[23] SUZUKI S,MIYASAKA K,JIMI A,et al.Induction of acute pancreatitis by cerulein in human IL-6 gene transgenic mice[J].Pancreas,2000,21(1):86-92.
[24] CUZZOCREA S,MAZZON E,DUGO L,et al.Absence of endogenous interleukin-6 enhances the inflammatory response during acute pancreatitis induced by cerulein in mice[J].Cytokine,2002,18(5):274-285.
[25] CHAO K C,CHAO K F,CHUANG C C,et al.Blockade of interleukin 6 accelerates acinar cell apoptosis and attenuates experimental acute pancreatitis in vivo[J].Br J Surg,2006,93(3):332-338.
[26] LESINA M,KURKOWSKI M,LUDES K,et al.Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer[J].Cancer Cell,2011,19(4):456-469.
[27] BRAGANZA J M,LEE S H,MCCLOY R F,et al.Chronic pancreatitis[J].Lancet,2011,377(9772):1184-1197.
[28] 赵永祥,吴向铭,张建国,等.中药清胰汤合剂对慢性胰腺炎中炎症因子IL-6的影响[J].内蒙古医学杂志,2016,48(4):430-431.
[29] 田珍珍,朱杰,王淑华,等.慢性胰腺炎患者胰腺和血清中TLR4信号通路关键因子的检测及其意义[J].吉林大学学报(医学版),2013,39(4):763-767.
[30] 李仕维,李乃民,张宏志,等.针药结合治疗肝郁脾虚血瘀型慢性胰腺炎疗效及对患者血清炎症因子的影响[J].针灸临床杂志,2018,34(9):12-15.
[31] DUAN L F,XU X F,ZHU L J,et al.Dachaihu decoction ameliorates pancreatic fibrosis by inhibiting macrophage infiltration in chronic pancreatitis[J].World J Gastroenterology,2017,23(40):7242-7252.
[32] MEWS P,PHILLIPS P,FAHMY R,et al.Pancreatic stellate cells respond to inflammatory cytokines:potential role in chronic pancreatitis[J].Gut,2002,50(4):535-541.
[33] AOKI H,OHNISHI H,HAMA K,et al.Existence of autocrine loop between interleukin-6 and tranforming growth factor-1 in activated rat pancreatic stellate cells[J].J Cell Biochem,2006,99(1):221-228.
[34] MARKUS M.JAK-STAT signaling in hepatic fibrosis[J].Front Biosci,2011,16(1):2794-2811.
[35] KNIGHT D,MUTSAERS S E,PRELE C M.STAT3 in tissue fibrosis:is there a role in the lung[J].Pulm Pharmacol Ther,2011,24(2):193-198.
[36] 朱林佳.大柴胡汤通过调控IL-6/STAT3信号通路对L-Arginine诱发CP胰腺纤维化的防治作用[D].咸阳:陕西中医药大学,2016.
[37] KOMAR H M,SERPA G,KERSCHER C,et al.Inhibition of JAK/STAT signaling reduces the activation of pancreatic stellate cells in vitro and limits caerulein-induced chronic pancreatitis in vivo[J].Sci Rep,2017,7(1):1787.
[38] 宗林飞.基于JAK2/STAT3通路的氧化苦参碱抗胰腺纤维化机制研究[D].唐山:华北理工大学,2016.
[39] KERN S E,SHI C,HRUBAN R H.The complexity of pancreatic ductal cancers and multidimensional strategies for therapeutic targeting[J].J Pathol,2011,223(2):295-306.
[40] MAITRA A,HRUBA N,RALPH H.Pancreatic cancer[J].Annu Rev Pathol,2008,3:157-188.
[41] STATHIS A,MOORE M J.Advanced pancreatic carcinoma:current treatment and future challenges[J].Nat Rev Clin Oncol,2010,7(3):163-172.
[42] CHANDANA S,BABIKER H,MAHADEVAN D,Therapeutic trends in pancreatic ductal adenocarcinoma (PDAC)[J].Expert Opin Investig Drugs,2019,28(2):161-177.
[43] KOZUKA S,SASSA R,TAKI T,et al.Relation of pancreatic duct hyperplasia to carcinoma[J].Cancer,1979,43(4):1418-1428.
[44] HRUBAN R H,TAKAORI K,KLIMSTRA D S,et al.An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms[J].Am J Surg Pathol,2004,28(8):977-987.
[45] HINGORANI S R,PETRICOIN E F,MAITRA A,et al.Preinvasive and invasive ductal pancreaticcancer and its early detection in the mouse[J].Cancer Cell,2003,4(6):437-450.
[46] PANG T C Y,WILSON J S,APTE M V.Pancreatic stellate cells:what′s new[J].Curr Opin Gastroenterol,2017,33(5):366-373.
[47] NAGATHIHALLI N S,CASTELLANOS J A,VANSAUN M N,et al.Pancreatic stellate cell secreted IL-6 stimulates STAT3 dependent invasiveness of pancreatic intraepithelial neoplasia and cancer cells[J].Oncotarget,2016,7(40):65982-65992.
[48] LANFREDINI S,THAPA A,O′NEILL E.RAS in pancreatic cancer[J].Biochem Soc Trans,2019,47(4):961-972.
[49] GREER J B,WHITCOMB D C.Inflammation and pancreatic cancer:an evidencebased review[J].Curr Opin Pharmacol,2009,9(4):411-418.
[50] RAZIDLO G L,BURTON K M,MCNIVEN M A.Interleukin-6 promotes pancreatic cancer cell migration by rapidly activating the small GTPase CDC42[J].J Biol Chem,2018,293(28):11143-11153.
[51] MACE T A,SHAKYA R,PITARRESI J R,et al.IL-6 and PD-L1 antibody blockade combination therapy reduces tumour progression in murine models of pancreatic cancer[J].Gut,2018,67(2):320-332.
[52] EBRAHIMI B,TUCKER S L,LI D,et al.Cytokines in pancreatic carcinoma:correlation with phenotypic characteristics and prognosis[J].Cancer,2004,101(12):2727-2736.
[53] MAYR M,SCHMID R M.Pancreatic cancer and depression:myth and truth[J].BMC Cancer,2010,10:569.
[54] HRUBAN R H,GOGGINS M,PARSONS J,et al.Progression model for pancreatic cancer[J].Clinical Cancer Res,2000,6(8):2969-2972.
[55] FUKUDA A,WANG S,JOHN P,et al.Stat3 and MMP7 contribute to pancreatic ductal adenocarcinoma initiation and progression[J].Cancer Cell,2011,19(4):441-455.
[56] LIU A,LIU Y,LI P K,et al.LLL12 inhibits endogenous and exogenous interleukin-6-induced STAT3 phosphorylation in human pancreatic cancer cells[J].Anticancer Res,2011,31(6):2029-2035.
[57] KLEIN B,CORRINGHAM R,TRIKHA M,et al.Targeted anti-interleukin-6 monoclonal antibody therapy for cancer:a review of the rationale and clinical evidence[J].Clin Cancer Res,2003,9(13):4653-4665.
[58] JONES S A,SCHELLER J,ROSE-JOHN S.Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling[J].J Clin Invest,2011,121(9):3375-3383.

相似文献/References:

[1]王佳贺,任开明,姜洪芳,等.肠致病性大肠杆菌毒力因子EspF对肿瘤坏死因子-α、白细胞介素-6 和白细胞介素-8的影响[J].新乡医学院学报,2011,28(03):265.
 WANG Jia-he,REN Kai-ming,JIANG Hong-fang,et al.Effect of virulence factor EspF from enteropathic E.coli on tumor necrosis factor-α,interleukin-6[J].Journal of Xinxiang Medical University,2011,28(12):265.
[2]张 慧,张 婷,宋 宇,等.薏苡仁对实验性腹腔粘连大鼠腹腔液炎性相关因子及粘连组织血管内皮生长因子、血管内皮标志物CD34表达的影响[J].新乡医学院学报,2014,31(10):792.[doi:10.7683/xxyxyxb.2014.10.006]
[3]李明超,邢 珊.早产儿脑损伤、母亲绒毛膜羊膜炎及脐动脉血白细胞介素-6水平的关系[J].新乡医学院学报,2016,33(10):875.[doi:10.7683/xxyxyxb.2016.10.010]
 LI Ming-chao,XING Shan.Relationship among brain injury of preterm infant,maternal chorioamnionitis and interleukin-6 level in umbilical artery blood[J].Journal of Xinxiang Medical University,2016,33(12):875.[doi:10.7683/xxyxyxb.2016.10.010]
[4]信 军,康 乐,张艺森,等.重组人促红细胞生成素对早产儿脑损伤的防治作用[J].新乡医学院学报,2018,35(10):928.[doi:10.7683/xxyxyxb.2018.10.020]
 XIN Jun,KANG Le,ZHANG Yi-sen,et al.Preventive effect of recombinant human erythropoietin on brain injury in premature infants[J].Journal of Xinxiang Medical University,2018,35(12):928.[doi:10.7683/xxyxyxb.2018.10.020]
[5]袁晓梅,高新愿,杨小花.脑源性神经营养因子、肿瘤坏死因子-α和白细胞介素-6与慢性阻塞性肺疾病患者急性加重后抑郁及预后的关系[J].新乡医学院学报,2020,37(4):355.[doi:10.7683/xxyxyxb.2020.04.012]
 YUAN Xiaomei,GAO Xinyuan,YANG Xiaohua.Correlation between brain-derived neurotrophic factor,tumor necrosis factor-α,interleukin-6 and the depressive state of chronic obstructive pulmonary disease patients after acute exacerbation[J].Journal of Xinxiang Medical University,2020,37(12):355.[doi:10.7683/xxyxyxb.2020.04.012]
[6]肖 莉,任 峰,李 冰,等.乳腺癌根治术患者术后血清抗酒石酸盐酸性磷酸酶5b和糖类抗原15-3及白细胞介素-6水平与骨转移的关系[J].新乡医学院学报,2020,37(5):441.[doi:10.7683/xxyxyxb.2020.05.010]
 XIAO Li,REN Feng,LI Bing,et al.Relationship between the levels of serum tartrate resistant acid phosphatase 5b,carbohydrate antigen 15-3,interleukin-6 and bone metastases in patients with breast cancer after radical mastectomy[J].Journal of Xinxiang Medical University,2020,37(12):441.[doi:10.7683/xxyxyxb.2020.05.010]
[7]项广宇.氯吡格雷联合阿托伐他汀钙治疗短暂性脑缺血发作疗效观察[J].新乡医学院学报,2019,36(1):081.[doi:10.7683/xxyxyxb.2019.01.018]
 XIANG Guang-yu.Effect of clopidogrel combined with atorvastatin calcium in the treatment of transient ischemic attack[J].Journal of Xinxiang Medical University,2019,36(12):081.[doi:10.7683/xxyxyxb.2019.01.018]
[8]姚 峰,何思泉,王妹芳,等.急性冠状动脉综合征患者经皮冠状动脉介入术后支架再狭窄与血浆内皮细胞膜微粒的相关性[J].新乡医学院学报,2021,38(3):245.[doi:10.7683/xxyxyxb.2021.03.008]
 YAO Feng,HE Siquan,WANG Meifang,et al.Correlation between plasma endothelial microparticles and stent restenosis after percutaneous coronary intervention of patients with acute coronary syndrome[J].Journal of Xinxiang Medical University,2021,38(12):245.[doi:10.7683/xxyxyxb.2021.03.008]
[9]黄盼盼,陈国荣.家族聚集性肺癌一家系报告[J].新乡医学院学报,2021,38(4):349.[doi:10.7683/xxyxyxb.2021.04.011]
 HUANG Panpan,CHEN Guorong.Familial cluster lung cancer family report[J].Journal of Xinxiang Medical University,2021,38(12):349.[doi:10.7683/xxyxyxb.2021.04.011]
[10]贾向红,刘亚博,周志敏.呼吸机相关性肺炎患者病原菌分布及血清降钙素原和白细胞介素-6水平对其预后的预测价值[J].新乡医学院学报,2021,38(12):1155.[doi:10.7683/xxyxyxb.2021.12.010]
 JIA Xianghong,LIU Yabo,ZHOU Zhimin.Distribution of pathogenic bacteria and the value of serum procalcitonin and interleukin-6 levels in predicting the prognosis of patients with ventilator-associated pneumonia[J].Journal of Xinxiang Medical University,2021,38(12):1155.[doi:10.7683/xxyxyxb.2021.12.010]

更新日期/Last Update: 2019-12-05