FIBROBLAST GROWTH-FACTOR INCREASES TNF-ALPHA-MEDIATED PROSTAGLANDIN-E(2) PRODUCTION AND TNF-ALPHA RECEPTOR EXPRESSION IN HUMAN FIBROBLASTS

To examine the possible role of basic fibroblast growth factor (FGF) in regulating the effects of TNFalpha, we tested the effect of FGF on TNFalpha-mediated PGE2 production and TNFalpha 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 TNFalpha between 3 and 11-fold. FGF stimulated TNFalpha-induced PGE2 production independent of potential TNFalpha-mediated IL-1 production, as neither anti-IL-1 mAbs nor IL-1 receptor antagonist protein (IRAP) inhibited TNFalpha 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 TNFalpha-induced PGE2 production; the maximal FGF effect was reached after a 6 h preincubation. We also found that FGF significantly enhanced TNFalpha receptor expression. Untreated fibroblasts expressed almost-equal-to 3,900 receptors/cell, while cells treated with FGF for 6 h expressed almost-equal-to 9,500 receptors/cell, a 2.4-fold increase in receptor number; there was no apparent change in affinity for TNFalpha (K(d) 3.8 x 10(-11) M). The FGF-mediated increase in TNFalpha receptor expression and TNFalpha-mediated PGE2 production could be abolished by FGF mAbs, indicating a specific FGF effect. These results show that FGF increases TNFalpha receptor expression and suggest that this may account, at least in part, for the ability of FGF to enhance TNFalpha-mediated PGE2 production in human fibroblasts.