Interaction between oncostatin M, interleukin 1 and prostaglandin E2 in induction of IL-6 expression in human fibroblasts.
The role of Oncostatin M (OM), a monocyte/macrophage and T-cell product, in regulating IL-6 expression in fibroblasts of lung or synovial origin was examined in vitro. Although by itself OM had a minimal effect on enhancing IL-6 production by fibroblasts, in combination with IL-1 alpha or PGE2, OM addition resulted in a dose-dependent synergistic enhancement of IL-6 production. This synergistic effect with either IL-1 alpha (5 ng/ml) or PGE2 (10(-7) M) was clearly evident at concentrations of OM of 10, 20 or 50 ng/ml. Levels of IL-6 resulting from OM and IL-1 alpha stimulation could be reduced by indomethacin (10(-6) M) and restored again by also adding PGE2. Northern blots probed for IL-6 mRNA showed cooperative enhancement of steady state levels at 18 hours of stimulation by OM and IL-1 alpha, or OM and PGE2. Probing for mRNA of the metalloproteinase inhibitor TIMP-1 showed that stimulation by OM, IL-1 alpha or PGE2 enhanced TIMP-1 levels. However, OM (alone) or PGE2 or both combined did not elevate the metalloproteinase stromelysin-1 mRNA signals. Analysis utilizing a rat IL-6 promoter-luciferase reporter gene construct showed that OM stimulation resulted in activation of transcription that synergistically enhanced IL-1-induced levels of reporter gene expression. These results show that although OM has minor effects on IL-6 production alone, the combination of OM and other mediators result in markedly enhanced IL-6 production by fibroblasts in vitro.
Richards
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CD
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Agro
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D000818:Animals; D001681:Biological Assay; D015152:Blotting, Northern; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis*; D007700:Kinetics; D008168:Lung; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000096:biosynthesis; D013583:Synovial Membrane; D019714:Tissue Inhibitor of Metalloproteinases; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D016207:Cytokines; D006023:Glycoproteins; D007375:Interleukin-1; D015850:Interleukin-6; C508351:OSM protein, human; D010455:Peptides; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D053683:Oncostatin M; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D015232:Dinoprostone