title: Modification of biological responses to interleukin-1 by agents that perturb signal transduction pathways.
abstract: In this study we have examined the effect of agents known to perturb certain signal transduction pathways on the biological responses of target cells to stimulation with interleukin-1 (IL-1). In the murine thymoma cell line EL4, IL-1 stimulation results in the secretion of interleukin-2 (IL-2), which was subsequently measured by proliferation of an IL-2-dependent cell line. Agents that elevated intracellular cAMP blocked or partially blocked IL-1 induction of IL-2 secretion, whereas agents that activated protein kinase C (PKC) resulted in a synergistic enhancement. Both pertussis and cholera toxins also inhibited IL-1-induced IL-2 secretion, although probably by acting at different levels. IL-1 simulation of human and murine fibroblasts resulted in release of prostaglandin E2. This response was inhibitable by pertussis toxin but not by cholera toxin, whereas co-stimulation of the fibroblasts with IL-1 and phorbol ester resulted in a synergistic response. Murine fibroblasts could also be stimulated to proliferate by IL-1, and this response was also inhibitable by pertussis toxin. These findings are consistent with coupling of the IL-1 receptor to a signalling pathway via a pertussis toxin substrate.
authors.affiliation: Department of Cellular Science, Glaxo Group Research Ltd., Greenford, Middlesex, UK.
authors.forename: P
authors.initials: P
authors.lastname: Rollins
authors.forename: S
authors.initials: S
authors.lastname: Witham
authors.forename: K
authors.initials: K
authors.lastname: Ray
authors.forename: N
authors.initials: N
authors.lastname: Thompson
authors.forename: H
authors.initials: H
authors.lastname: Sadler
authors.forename: N
authors.initials: N
authors.lastname: Smithers
authors.forename: S
authors.initials: S
authors.lastname: Grenfell
authors.forename: R
authors.initials: R
authors.lastname: Solari
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D004075:Diglycerides / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D005434:Flow Cytometry; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D004075:Diglycerides; D007375:Interleukin-1; D007376:Interleukin-2; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; C044295:1,2-dioctanoylglycerol; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine