目的:初步探讨白细胞介素-34(IL-34)对类风湿关节炎(RA)患者成纤维细胞样滑膜细胞(FLS)CC趋化因子配体28(CCL28)表达的影响.方法:选取6例RA患者关节滑膜分离并培养FLS,分别用IL-34、IL-34受体拮抗剂/IL-34、信号通路抑制剂/IL-34刺激.采用反转录聚合酶链式反应(RT-PCR)检测 FLS CCL28 mRNA的表达;酶联免疫吸附试验(ELISA)检测细胞培养上清中CCL28水平.两组间比较采用t检验.结果:与对照组相比,IL-34刺激后FLS分泌CCL28增多(P<0.05);加入IL-34受体拮抗剂后FLS分泌CCL28水平降低(P<0.05);细胞培养体系中加入核因子-κB(NF-κB)、丝裂原活化蛋白激酶38(p38 MAPK)信号通路抑制剂后,CCL28表达明显降低(P<0.05).结论:IL-34与其受体结合可能通过激活NF-κB和p38 MAPK信号通路促进RA FLS分泌CCL28,从而参与RA的发病过程.
Objective:To investigate the effects of interleukin-34(IL-34)on the expression of CC chemokine ligand 28 (CCL28) by fibroblast-like synoviocytes(FLS) in rheumatoid arthritis(RA) patients.Methods:FLS were isolated from 6 RA patients and stimulated with IL-34,IL-34 receptor antagonist /IL-34,inhibitors of signaling pathway/IL-34 in vitro respectively.CCL28 mRNA expression was measured by reverse transcription polymerase chain reaction(RT-PCR).The level of CCL28 in the supernatant of RA FLS culture was detected by enzyme linked immunosorbent assay(ELISA).Statistical analysis between groups was performed by t test.Results:Compared with unstimulated FLS,CCL28 expression was increased obviously in IL-34-stimulated group(P<0.05).The level of CCL28 was significantly decreased when anti-IL-34 antibody was added into IL-34-administrated RA FLS(P<0.05).While after adding of nuclear factor κB(NF-κB) and mitogen-activated protein kinase38(p38 MAPK) signaling pathway inhibitors into the cell culture system,CCL28 expression was remarkably reduced (P<0.05).Conclusion: The secretion of CCL28 by RA FLS can be promoted by the binding of IL-34 with its specific receptor via the activation of NF-κB and p38 MAPK signaling pathways,which suggests that CCL28 might be involved in the pathogenesis of RA.
欧阳寻丽;李寒;孙晓彤;张彦;李霞;魏晶
医药卫生
类风湿关节炎;白细胞介素-34;成纤维样滑膜细胞;CC趋化因子配体28
Rheumatoid arthritis;Interleukin-34;Fibroblast-like synoviocytes;CC chemokine ligand 28
《中国免疫学杂志》 2018 (002)
239-242 / 4
本文受国家自然科学基金面上项目(81373214,8167606)、大连医科大学转化医学专项基金资助项目(2015010)和大连医科大学基础医学学科"青年教师助飞计划"项目资助.
10.3969/j.issn.1000-484X.2018.02.016
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