Reyes Lilian I, León Francisca, González Patricia, Rozas María F, Labarca Cristián, Segovia Alejandra, Neira Oscar, Naves Rodrigo
Instituto de Ciencias, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo. Av. Las Condes 12438, Lo Barnechea, Santiago, Chile.
Clínica Alemana, Av. Vitacura 5951, Vitacura, Santiago, Chile; Hospital Padre Hurtado, Esperanza 2150, San Ramón, Santiago, Chile.
Cytokine. 2008 May;42(2):170-178. doi: 10.1016/j.cyto.2007.12.005. Epub 2008 Mar 7.
Fibroblast-like synoviocytes (FLS) play a major role in the pathogenesis of rheumatoid arthritis (RA). FLS isolated from patients with RA (FLS-RA) express B cell-activating factor belonging to the TNF family (BAFF), a cytokine that has been associated with the onset and progression of RA. Glucocorticoids are powerful anti-inflammatory drugs used in the treatment of RA. In the present study, we examined the effect of dexamethasone (Dex) on constitutive and TNF-alpha- and IFN-gamma-induced BAFF expression in FLS-RA. BAFF mRNA expression and soluble BAFF were determined by RT-PCR and ELISA, respectively. The results showed that constitutive BAFF mRNA expression was inhibited by Dex in a dose- and time-dependent manner. Also, Dex inhibited the secretion of BAFF in a time-dependent manner reaching 76% of inhibition 72 h after treatment. Moreover, Dex suppressed both mRNA and protein BAFF expression induced by TNF-alpha but had no effect on IFN-gamma-induced BAFF expression. In comparison with B cells cultured alone, B cells co-cultured with FLS-RA exhibited a higher survival, which was inhibited when FLS-RA were pretreated with Dex. However, the enhanced B cell survival was reestablished by the addition of rhBAFF. Therefore, Dex is a potent inhibitor of constitutive and TNF-alpha-induced BAFF expression in FLS-RA.
成纤维样滑膜细胞（FLS）在类风湿关节炎（RA）的发病机制中起主要作用。从RA患者中分离出的FLS（FLS-RA）表达属于肿瘤坏死因子家族的B细胞活化因子（BAFF），该细胞因子与RA的发病和进展有关。糖皮质激素是用于治疗RA的强效抗炎药物。在本研究中，我们检测了地塞米松（Dex）对FLS-RA中组成型以及肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）诱导的BAFF表达的影响。分别通过逆转录聚合酶链反应（RT-PCR）和酶联免疫吸附测定（ELISA）来测定BAFF信使核糖核酸（mRNA）表达和可溶性BAFF。结果显示，Dex以剂量和时间依赖性方式抑制组成型BAFF mRNA表达。此外，Dex以时间依赖性方式抑制BAFF的分泌，在处理后72小时达到76%的抑制率。而且，Dex抑制TNF-α诱导的BAFF mRNA和蛋白表达，但对IFN-γ诱导的BAFF表达没有影响。与单独培养的B细胞相比，与FLS-RA共培养的B细胞具有更高的存活率，当FLS-RA用Dex预处理时，该存活率受到抑制。然而，通过添加重组人BAFF（rhBAFF）可恢复增强的B细胞存活率。因此，Dex是FLS-RA中组成型和TNF-α诱导的BAFF表达的有效抑制剂。
