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

Biochem Biophys Res Commun. 1999 Apr 13;257(2):528-32. doi: 10.1006/bbrc.1999.0523.

Abstract

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 E2 (PGE2) production in human gingival fibroblasts stimulated by interleukin-1beta (IL-1beta) and/or epidermal growth factor (EGF). The cytokine IL-1beta and to a lesser extent EGF, enhanced COX-2 mRNA levels in gingival fibroblasts. Simultaneous treatment with EGF and IL-1beta resulted in enhanced COX-2 mRNA levels accompanied by a synergistic stimulation of PGE2 biosynthesis compared to the cells treated with IL-1beta or EGF alone. Neither IL-1beta EGF nor the combination of IL-1beta 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 PGE2 production induced by IL-1beta or the combination of IL-1beta and EGF whereas COX-1 mRNA levels were not affected. Furthermore, the COX-2 specific inhibitor, NS-398, abolished the PGE2 production induced by IL-1beta, EGF, or the combination. These results indicate that the synergy between IL-1beta and EGF on PGE2 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoquinones
  • Cells, Cultured
  • Child
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Dinoprostone / biosynthesis*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Epidermal Growth Factor / antagonists & inhibitors
  • Epidermal Growth Factor / pharmacology*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression Regulation / drug effects
  • Gingiva / drug effects*
  • Gingiva / metabolism
  • Humans
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / pharmacology*
  • Isoenzymes / genetics
  • Lactams, Macrocyclic
  • Membrane Proteins
  • Nitrobenzenes / pharmacology
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism*
  • Quinazolines / pharmacology
  • Quinones / pharmacology
  • RNA, Messenger / metabolism
  • Rifabutin / analogs & derivatives
  • Sulfonamides / pharmacology
  • Time Factors

Substances

  • Benzoquinones
  • Interleukin-1
  • Isoenzymes
  • Lactams, Macrocyclic
  • Membrane Proteins
  • Nitrobenzenes
  • Quinazolines
  • Quinones
  • RNA, Messenger
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Rifabutin
  • Epidermal Growth Factor
  • herbimycin
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Protein-Tyrosine Kinases
  • Dinoprostone
  • 4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline