Fibroblast growth factor increases TNF?-mediated prostaglandin E2 production and TNF? receptor expression in human fibroblasts

Publisher Website
Google Scholar
Abstract
To examine the possible role of basic fibroblast growth factor (FGF) in regulating the effects of TNFα, we tested the effect of FGF on TNFα-mediated PGE2 production and TNFα receptor expression in human fibroblasts. We found that, while FGF alone had no effect on PGE2 production, it enhanced the amount of PGE2 produced in response to TNFα between 3 and 11-fold. FGF stimulated TNFα-induced PGE2 production independent of potential TNFα-mediated IL-1 production, as neither anti-IL-1 mAbs nor IL-1 receptor antagonist protein (IRAP) inhibited TNFα induced-PGE2 production or the stimulatory effect of FGF. A one minute exposure of cells to FGF prior to removal was sufficient to significantly enhance TNFα-induced PGE2 production; the maximal FGF effect was reached after a 6 h preincubation. We also found that FGF significantly enhanced TNFα receptor expression. Untreated fibroblasts expressed ≈3,900 receptors/cell, while cells treated with FGF for 6h expressed ≈9,500 receptors/cell, a 2.4-fold increase in receptor number; there was no apparent change in affinity for TNFα (Kd 3.8×10−11 M). The FGF-mediated increase in TNFα receptor expression and TNFα-mediated PGE2 production could be abolished by FGF mAbs, indicating a specific FGF effect. These results show that FGF increases TNFα receptor expression and suggest that this may account, at least in part, for the ability of FGF to enhance TNFα-mediated PGE2 production in human fibroblasts.