TNF-α、IL-1β通过PKA通路诱导成纤维样滑膜细胞中力生长因子表达  

TNF-α,IL-1β induce mechano growth factor expression in human fibroblast-like synoviocytes through the PKA pathway

作　　者：黄杨河[1] 罗自维[1] 李海滨[1] 吴双迟 吕永钢[1] 刘万钱[1] 钟莉[1] 杨力[1] 

机构地区：[1]重庆大学生物工程学院生物流变科学与技术教育部重点实验室国家“111计划”基地,重庆400044

出　　处：《医用生物力学》2014年第3期276-280,共5页Journal of Medical Biomechanics

基　　金：高等学校学科创新引智计划(国家“111计划”)(B06023);国家自然科学基金资助项目(11032012,31270990);新世纪优秀人才支持计划(NCET-10-0879);重庆大学大型仪器设备开放基金

摘　　要：目的探讨炎症因子TNF-α、IL-1β、IL-6对力生长因子(mechano growth factor,MGF)表达的影响。方法实验组细胞用浓度为25、50、100 ng/mL的TNF-α、IL-6或者是2.5、5.0、10 ng/mL的IL-1β处理12 h,抑制剂组在因子处理前用1.0 mmol KT5720预处理1 h,然后添加炎症因子刺激12 h,对照组细胞保持与实验组培养条件一致的情况下不添加因子刺激。因子刺激后,用定量PCR方法检测细胞中MGF表达量。结果 25 ng/mL TNF-α和10 ng/mL IL-1β因子刺激滑膜成纤维细胞诱导MGF表达显著增加(P<0.05)。IL-6对MGF表达无影响。1.0 mmol PKA通路抑制剂KT5720处理显著降低TNF-α和IL-1β诱导的MGF表达(P<0.05)。结论炎症因子TNF-α和IL-1β在浓度分别为25和10 ng/mL时能显著诱导滑膜成纤维细胞中MGF表达,其表达是通过PKA通路介导的。本研究对于促进MGF用于改善膝关节相关组织修复中的应力刺激不足有一定的现实意义。Objective To investigate the effects of inflammatory factors TNF-α, IL-1β, IL-6 on expression of mechano growth factor （MGF）. Methods In the experimental group, TNF-α and IL-6 at concentration of 25, 50, 100 ng/mL, or IL-1β at concentration of 2.5, 5.0, 10 ng/mL were applied to fibroblast-like synoviocytes （FLSs） for 12 hours. The inhibitor groups were pretreated with PKA pathway inhibitor KT5720 at concentration of 1.0 mmol for 1 hour. The control group remained under the same culture condition as the experimental group, but without any growth factor. Real-time PCR was used to measure the gene expression of MGF. Results Treated with TNF-α at concentration of 25 ng/mL and IL-1β at concentration of 10 ng/mL, the MGF expression in FLSs was significantly increased （P 〈0.05）. IL-6 had no effect on MGF expression. A specific inhibitor of cAMP-dependent protein kinase, at concentration of 1.0 mmol significantly decreased the activation of MGF synthesis by TNF-α and IL-1β in FLSs （ P 〈 0.05 ）. Conclusions TNF-α at concentration of 25 ng/mL and IL-1β at concentration of 10 ng/mL significantly induce the MGF expression in FLSs, which activate MGF synthesis via the PKA pathway. This study is of significance in improving the application of MGF used in tissue repair area to make up the insufficient stress stimulation.

关 键 词：力生长因子 成纤维样滑膜细胞 应力刺激 

分 类 号：R318.01[医药卫生—生物医学工程]