Interleukin-1 alpha-stimulated fibroblast eicosanoid synthesis is not mediated by interleukin-6.
Adherent human dermal fibroblasts secreted interleukin-6, prostaglandin E2, prostaglandin I2 and 15-hydroxyeicosatetraenoic acid (assayed by radioimmunoassay) during a 3 h incubation period. Although human dermal fibroblasts did not secrete interleukin-1 alpha or interleukin-1 beta, human recombinant interleukin-1 alpha stimulated arachidonic acid metabolism and interleukin-6 synthesis. This effect was, at least partly, dependent on de novo protein synthesis. In contrast, human recombinant interleukin-6 had no effect on the synthesis and release of the eicosanoids measured. Human recombinant interleukin-1 alpha also stimulated the metabolism of [14C]arachidonic acid, but only if fibroblast were pre-incubated with the cytokine for three hours. Our data indicate that (a) fibroblasts secrete interleukin-6 but not interleukin-1, (b) interleukin-1 alpha, but not interleukin-6, stimulates fibroblast arachidonic acid metabolism and (c) the mechanisms involved in the metabolism of endogenous arachidonic acid are more sensitive to human recombinant interleukin-1 alpha than those involved in metabolism of the exogenous substrate.
Elliott
G R
GR
Department of Pharmacology, Medical Biological Laboratory, T.N.O., Rijswijk, Netherlands.
Van de Meent
D
D
Van Dijk
J
J
D016718:Arachidonic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D015777:Eicosanoids / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism
D015777:Eicosanoids; D007375:Interleukin-1; D015850:Interleukin-6; D016718:Arachidonic Acid; D003513:Cycloheximide