TL1A促进类风湿关节炎患者成纤维样滑膜细胞分泌PGE_2

TL1A enhances PGE_2 expression by fibroblast-like synoviocytes in patients with rheumatoid arthritis

为了探讨肿瘤坏死因子样配体1A(TL1A)对类风湿关节炎(RA)患者成纤维样滑膜细胞(FLS)分泌前列腺素E2(PGE2)的影响,分离培养6例RA FLS,并分别用TL1A、肿瘤坏死因子受体(TNFR)拮抗剂(0.25μg/ml)加TL1A(50ng/ml)以及信号通路抑制剂(10μmol/L)加TL1A(50ng/ml)刺激。采用反转录聚合酶链式反应(RT-PCR)检测RA FLS Cox-2mRNA的表达;采用酶联免疫吸附试验(ELISA)检测RA FLS培养上清液中PGE2的水平。统计学方法采用t检验。结果显示,与未刺激组相比,TL1A刺激的RA FLS Cox-2mRNA和PGE2表达均增多(P<0.05);加入TNFR2拮抗剂可使TL1A刺激的RA FLS分泌PGE2水平显著降低(P<0.05)。此外,细胞培养体系加入NF-κB和JNK抑制剂后,TL1A刺激RA FLS产生PGE2水平明显下降(P<0.05)。研究表明,TL1A与TNFR2结合可能通过NF-κB和JNK信号通路促进RA FLS分泌PGE2,参与RA的发病过程。

To investigate the effects of TNF-like cytokine I A（TL1A） on prostaglandin E2 （PGE2） secreted by fibroblast-like synoviocytes（FLS） in patients with rheumatoid arthrltis（RA）. RA FLS was isolated from 6 RA patients and cultured in vitro. RA FLS was stimulated with TLIA（50 ng/ml）, antagonist of tumor necrosis factor reeeptor（TNFR）（0.25 pg/ml）/TL1A（50 ng/ml） and inhibltors of signaling pathway（10 μmol/L）/TL1A（50 ng/ml）, respectively. The expression of Cox-2 mRNA was detected by reverse transcription polymerase chain reaetion（RT-PCR）. The level of PGE2 in the supernatant of RA FLS culture was measured by Enzyme linked immunosorbent assay（F-LISA）. Statistical analysis was performed by t test. Compared to uns- timulated RA FLS, TL1A-stimulated RA FLS had significantly increased expression of Cox-2 mRNA and PGE2 （P 〈 0.05）. The level of PGEz was significantly decreased when anti-TNFR2 antibody was added to the TL1A -stimulated RA FLS（P〈0. 05）. Moreover, in the presence of IKK-16 and 8P600125, the level of PGE2 produced by TL1A-stimulated FLS was obviously deereased（P〈0.05）. The research shows that the combination of TL1A and TNFR2 may upregulate the secretion of RA FLS via NF-kB and JNK signaling pathway, suggesting that it might be involved in the pathogenesis of RA.