期刊文献+

八肽胆囊收缩素对TNF-α诱导的大鼠滑膜细胞株RSC-364 IL-6的作用及其可能的分子机制(英文) 被引量:8

Effects of cholecystokinin octapeptide on TNF-α-induced IL-6 expression and its possible molecular mechanism in rat synovial cell strain RSC-364
下载PDF
导出
摘要 目的:观察硫酸化八肽胆囊收缩素(sCCK -8)对TNF-α诱导大鼠滑膜细胞株RSC -364 IL-6mRNA表达及核因子NF-κB的影响及其可能的受体机制。方法:大鼠滑膜细胞株RSC -364经TNF-α(10μg/L)、sCCK-8(10-8-10-6mol/L)、CCK受体拮抗剂丙谷胺(2 mg/L)及溶剂单独或联合孵育3 h,用RT-PCR检测细胞IL-6、CCK-AR及CCK-BR mRNA的表达,孵育1 h,用电泳迁移率检测NF-κB活性,孵育30min,用Western blot-ting检测胞浆IκB蛋白表达。结果:RSC -364细胞固有表达CCK-A/B受体,sCCK-8(10-8-10-6mol/L)使IL-6、CCK-AR和CCK-BR mRNA表达进一步增高,明显增加TNF-α诱导的NF-κB活性,降低胞浆中IκB蛋白水平,并可被丙谷胺所拮抗。结论:sCCK-8通过NF-κB途径上调TNF-α诱导的大鼠滑膜细胞IL-6 mRNA表达,此作用可能通过滑膜细胞上的CCK受体实现,提示CCK-8在类风湿性关节炎(RA)发病过程中可能具有调控作用。 AIM: To investigate the effect of sulfated cholecystokinin octapeptide (CCK -8 ) on TNF -α induced IL - 6 mRNA expression, NF - κB activation in the rat fibroblast - like synovial cell strain RSC - 364 and its possible receptor mechanisms. METHODS: RSC -364 cells were stimulated with TNF - α( 10 μg/L) in the presence or absence of sCCK- 8( 10-8 - 10-6 mol/L) or/and CCK receptor antagonist proglumide(2 mg/L). IL -6 and CCK receptor A/B (CCK- AR/CCK/BR) mRNA expression were assayed by reverse transcription polymerase chain reaction (RT- PCR) at 3 h after stimulation, and nuclear factor - κB (NF - κB) binding activity was analyzed by electrophoretic mobility shift assay (EMSA) at lh after stimulation. At 30 min of stimulation the IκB protein level in cytoplasma was measured by Western blotting. RESULTS: Both CCK - AR and CCK - BR were constitutively expressed on RSC - 364. sCCK - 8, at concentrations from 10-8 mol/L to 10 -6 mol/L, significantly increased IL - 6 mRNA expression, CCK - AR and CCK - BR mRNA expression, NF - κB binding activity and IκB protein degradation. The effects of sCCK - 8 on NF - κB activity and IκB degradation level were attenuated by CCK receptor antagonist proglumide. CONCLUSION: sCCK - 8 upregulats TNF - α- induced IL - 6 mRNA expression by NF - κB pathway through its receptor on rat synoviocytes, suggesting its possible regulatory role in the pathogenesis of rheumatoid arthritis.
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2007年第7期1396-1401,共6页 Chinese Journal of Pathophysiology
基金 Supported by the National Nature Science Foundation of China(No 30470679)
关键词 关节炎 类风湿 胆囊收缩素 滑膜细胞 白细胞介素6 NF—κB Arthritis, rheumatoid Choleeystokinin Synoviocytes Interleukin - 6 NF - kappa B
  • 相关文献

参考文献15

  • 1Juarranz Y,Abad C,Martinez C,et al.Protective effect of vasoactive intestinal peptide on bone destruction in the collagen-induced arthritis model of rheumatoid arthritis[J].Arthritis Res Ther,2005,7(5):R1034-R1045.
  • 2Manni L,Lundeberg T,Tirassa P,et al.Role of cholecystokinin -8 in nerve growth factor and nerve growth factor mRNA expression in carrageenan-induced joint inflammation in adult rats[J].Rheumatology,2002,41(7):787-792.
  • 3Liu S,Khemlani LS,Shapiro RA,et al.Expression of CD14 by hepatocytes:upregulation by cytokines during endotoxemia[J].Infect Immun,1998,66 (11):5089 -5098.
  • 4Deon D,Ahmed S,Tai K,et al.Cross -talk between IL-1 and IL-6 signaling pathways in rheumatoid arthritis synovial fibroblasts[J].J Immunol,2001,167(9):5395-5403.
  • 5Nishimoto N,Kishimoto T,Yoshizaki K.Anti-interleukin 6 receptor antibody treatment in rheumatic disease[J].Ann Rheum Dis,2000,59(Suppl):i21 -i27.
  • 6Hirth A,Skapenko A,Kinne RW,et al.Cytokine mRNA and protein expression in primary-cultrue and repeatedpassage synovial fibroblasts from patients with rheumatoid arthritis[J].Arthritis Res,2002,4(2):117-125.
  • 7Ji H,Pettit A,Ohmura K,et al.Critical roles for interleukin 1 and tumor necrosis factor α in antibody-induced arthritis[J].J Exp Med,2002,196(1):77 -85.
  • 8Nishimoto N,Ito A,Ono M,et al.IL-6 inhibits the proliferation of fibroblastic synovial cells from rheumatoid arthritis patients in the presence of soluble IL -6 receptor[J].Int Immunol,2000,12(2):187-193.
  • 9Ernst M,Inglese M,Waring P,et al.Defective gp130-mediated signal transducer and activator of transcription(STAT) signaling results in degenerative joint disease,gastrointestinal ulceration,and failure of uterine implantation[J].J Exp Med,2001,194(2):189 -203.
  • 10Feldmann M,Andreakos E,Smith C,et al.Is NF-κB a useful therapeutic target in rheumatoid arthritis?[J].Ann Rheum Dis,2002,61(Suppl Ⅱ):ii13 -ii18.

同被引文献106

引证文献8

二级引证文献65

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部