Involvement of tyrosine kinases on cyclooxygenase expression and prostaglandin E2 production in human gingival fibroblasts stimulated with interleukin-1β and epidermal growth factor

The purpose of the present study was to investigate the involvement of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and tyrosine kinase on prostaglandin E-2 (PGE(2)) production in human gingival fibroblasts stimulated by interleukin-1 beta (IL-1 beta) and/or epidermal growth factor (EGF). The cytokine IL-1 beta and to a lesser extent EGF, enhanced COX-2 mRNA levels in gingival fibroblasts. Simultaneous treatment with EGF and IL-1 beta resulted in enhanced COX-2 mRNA levels accompanied by a synergistic stimulation of PGE(2) biosynthesis compared to the cells treated with IL-1 beta or EGF alone. Neither IL-1 beta EGF nor the combination of IL-1 beta and EGF enhanced COX-1 mRNA levels in gingival fibroblasts. The tyrosine kinase inhibitors, Herbimycin A and PD 153035 hydrochloride, reduced COX-2 mRNA levels as well as PGE(2) production induced by IL-1 beta or the combination of IL-1 beta and EGF whereas COX-1 mRNA levels were not affected. Furthermore, the COX-2 specific inhibitor, NS-398, abolished the PGE(2) production induced by IL-1 beta, EGF, or the combination. These results indicate that the synergy between IL-1 beta and EGF on PGE(2) production is due to an enhanced gene expression of COX-2 and that tyrosine kinase(s) are involved in the signal transduction of COX-2 in gingival fibroblasts. (C) 1999 Academic Press.