BRMS1通过下调NF-κB核转位抑制成纤维样滑膜细胞分泌IL-1β

BRMS1 inhibit IL- 1β secretion in synovial cell fibroblasts by suppress the nuclear translocation of NF-κB

目的探讨乳腺癌转移抑制蛋白1(BRMS1)对人类风湿性关节炎(RA)的成纤维样滑膜细胞(FLS)分泌IL-1β的影响和机制。方法分别取4例RA患者膝关节滑膜组织及1例正常人(normal)膝关节滑膜组织,采用组织贴壁法分离FLS。用慢病毒法过表达BRMS1蛋白。Western blot检测BRMS1蛋白及核蛋白NF-κB水平,Elisa法检测细胞培养基中IL-1β水平,免疫荧光检测NF-κB核转位。结果 RA组FLS的BRMS1蛋白表达较N组明显下调,但NF-κB核转位明显增加、IL-1β分泌明显增加。RA组FLS过表达BRMS1后,FLS核蛋白中NF-κB表达明显减少、IL-1β分泌下降。LPS诱导的NF-κB核转位和IL-1β表达增加被过表达BRMS1明显抑制。结论 BRMS1可以抑制NF-κB核转位,从而减少成纤维样滑膜细胞分泌IL-1β。

Objective To investigate the effects and mechanism of breast cancer metastasis suppressor 1(BRMS1) in IL- 1βsecretion of fibroblast- like synovial cells(FLS) in rheumatoid arthritis(RA). Methods The synovial membrane tissues were obtained from 4 RA patients and 1 healthy subject and FLS were isolated by means of tissue culture. FLS were transfected with lenti-virus with BRMS1 protein. BRMS1 protein and nuclear protein NF-κB were detected by Western blot, IL-1β secretion was estimated by Elisa and nuclear translocation of NF-k B was observed by immunofluorescence. Results The BRMS1 protein was obviously decreased in RA group than normal group, but nuclear protein NF- κB and IL- 1β secretion were increased significantly. Nuclear protein NF- κB and IL- 1β secretion were obviously downregulated in the FLS with BRMS1 protein overexpression of RA group. LPS induced nuclear translocation of NF- κB and IL- 1β secretion were obviously inhibited by BRMS1. Conclusion BRMS1 could suppress the nuclear translocation of NF-κB and then reduce the IL-1β secretion of FLS.