Differential effect of IL-1β and TNF-α on the production of IL-6, IL-8 and PGE2 in fibroblast-like synoviocytes and THP-1 macrophages
Differential effect of IL-1β and TNF-α on the production of IL-6, IL-8 and PGE2 in fibroblast-like synoviocytes and THP-1 macrophages
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DOI：
10.1007/s00296-009-1089-y
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发表时间：
2010-06-01
影响因子：
4
通讯作者：
Kim, Kyoung Soo
中科院分区：
文献类型：
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作者：
Choi, Hyun Mi;Oh, Da Hee;Kim, Kyoung Soo
类风湿关节炎关节炎症是一种复杂的免疫反应，受多种因素的影响，如细胞因子、细胞、缺氧等。因此，我们评估了成纤维细胞样滑膜细胞（FLSs）和巨噬细胞在缺氧或常氧条件下产生促炎介质以响应IL-1 β、tnf - α或IL-17的相对能力。IL-6在FLSs和THP-1巨噬细胞中的表达水平均因IL-1 β和tnf - α而显著升高，但tnf - α的表达水平低于IL-1 β的表达水平。相反，IL-8在两种细胞类型中的表达均受到IL-1 β和tnf - α的强烈刺激。在FLSs中，PGE(2)的产生仅对IL-1 β有反应；在THP-1细胞和tnf - α刺激的FLSs中未观察到任何影响。此外，与IL-1 β或tnf - α诱导的FLSs和THP-1细胞相比，IL-17的产生极低。低氧（2% O-2）降低IL-1 β刺激的PGE产生(2)，尽管它增加了COX-2 mRNA和蛋白的表达。这些结果表明，IL-1 β和tnf - α在低氧和常氧条件下对FLSs和巨噬细胞基因表达的调节存在差异。
Inflammation in the joint of rheumatoid arthritis is a complex immune reaction facilitated by various factors, such as cytokines, cells and hypoxia. Thus, we evaluated their relative capacity to produce proinflammatory mediators in response to IL-1 beta, TNF-alpha or IL-17 under hypoxia or normoxia in fibroblast-like synoviocytes (FLSs) and macrophages. The level of IL-6 expression was strongly increased in both FLSs and THP-1 macrophages in response to IL-1 beta and TNF-alpha, but the level by TNF-alpha was less than that by IL-1 beta. In contrast, the expression of IL-8 in both cell types was strongly stimulated by both IL-1 beta and TNF-alpha. In FLSs, PGE(2) production increased only in response to IL-1 beta; and no effect was observed in THP-1 cells and TNF-alpha-stimulated FLSs. In addition, the production by IL-17 was extremely low when compared with those induced by IL-1 beta or TNF-alpha in FLSs and THP-1 cells. Hypoxia (2% O-2) decreased IL-1 beta-stimulated production of PGE(2), even though it increased the expression of mRNA and protein of COX-2. These results suggest that IL-1 beta and TNF-alpha differentially regulate gene expression in FLSs and macrophages under hypoxia or normoxia.