title: Epidermal growth factor potentiates interleukin 1 and tumor necrosis factor-induced prostaglandin biosynthesis in human gingival fibroblasts.
abstract: The effects of and interactions between epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha) interleukin 1 (IL-1) and tumour necrosis factor alpha (TNF-alpha) on arachidonic acid release and prostaglandin biosynthesis in human gingival fibroblasts were studied. IL-1 alpha, IL-1 beta and TNF-alpha, but not EGF nor TGF-alpha, stimulated prostaglandin E2 (PGE2) formation in the gingival fibroblasts. The effect of IL-1 alpha, IL-1 beta and TNF-alpha on PGE2 formation was significantly potentiated by EGF in a dose-dependent manner. Similarly, TGF-alpha synergistically potentiated IL-1 beta stimulated PGE2 formation. IL-1 beta but not EGF stimulated the release of 3H-arachidonic acid (3H-AA) from prelabelled gingival fibroblasts. In contrast to the effect on PGE2 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 PGE2 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-alpha act in concert to enhance prostanoid formation in gingival fibroblasts. Data indicates that EGF potentiates the IL-1 and TNF-alpha induced PGE2 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.
authors.affiliation: Department of Pedodontics, Karolinska Institutet, Huddinge, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Modéer
authors.forename: T
authors.initials: T
authors.lastname: Yucel-Lindberg
authors.forename: M
authors.initials: M
authors.lastname: Iinuma
authors.forename: U H
authors.initials: UH
authors.lastname: Lerner
authors.forename: G
authors.initials: G
authors.lastname: Andersson
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005881:Gingiva / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D004815:Epidermal Growth Factor; D015232:Dinoprostone