Differential effect of IL-1β and TNFα on the production of IL-6, IL-8 and PGE2 in fibroblast-like synoviocytes and THP-1 macrophages.

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-1beta, 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-1beta and TNF-alpha, but the level by TNF-alpha was less than that by IL-1beta. In contrast, the expression of IL-8 in both cell types was strongly stimulated by both IL-1beta and TNF-alpha. In FLSs, PGE(2) production increased only in response to IL-1beta; 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-1beta or TNF-alpha in FLSs and THP-1 cells. Hypoxia (2% O(2)) decreased IL-1beta-stimulated production of PGE(2), even though it increased the expression of mRNA and protein of COX-2. These results suggest that IL-1beta and TNF-alpha differentially regulate gene expression in FLSs and macrophages under hypoxia or normoxia.