Epidermal growth factor potentiates interleukin 1 and tumour necrosis factor-induced prostaglandin biosynthesis in human gingival fibroblasts

Abstract The effects of and interactions between epidermal growth factor (EGF), transforming growth factor α (TGF-α) interleukin 1 (IL-1) and tumour necrosis factor α (TNF-α) on arachidonic acid release and prostaglandin biosynthesis in human gingival fibroblasts were studied. IL-1α, IL-1β and TNF-α, but not EGF nor TGF-α, stimulated prostaglandin E 2 (PGE 2 ) formation in the gingival fibroblasts. The effect of IL-1α, IL-1β and TNF-α on PGE 2 formation was significantly potentiated by EGF in a dose-dependent manner. Similary, TGF-α synergistically potentiated IL-1β stimulated PGE 2 formation. IL-1β but not EGF stimulated the release of 3 H-arachidonic acid ( 3 H-AA) from prelabelled gingival fibroblasts. In contrast to the effect on PGE 2 formation, no synergistic interaction between EGF and IL-1 was seen on arachidonic acid (AA) release. Addition of unlabelled exogenous AA, in the presence of EGF, resulted in a significant increase in PGE 2 formation compared to that seen in fibroblasts not exposed to EGF. The results demonstrate that EGF and IL-1 as well as EGF and TNF-α act in concert to enhance prostanoid formation in gingival fibroblasts. Data indicates that EGF potentiates the IL-1 and TNF-α induced PGE 2 formation at the level of prostaglandin endoperoxide synthase (cyclooxygenase). The synergistic effects of inflammatory cytokines and growth factors may be of physiological importance for regulation of regenerative tissue growth during inflammation and repair.