title: Stimulation of human synovial fibroblast DNA synthesis by recombinant human cytokines.
abstract: The pronounced synovial hyperplasia often found in rheumatoid joints can be explained at least partially, by the interaction of monocyte-macrophage polypeptides (monokines) and lymphocyte polypeptides (lymphokines) with synovial fibroblast-like cells. We now report that purified recombinant human cytokines, interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor alpha, tumor necrosis factor beta (or lymphotoxin) and, to a variable extent, interferon-gamma, stimulate the DNA synthesis of human synovial fibroblast-like cells cultured in low (i.e., 1%) fetal bovine serum. With the exception of interferon-gamma, the effects of the cytokines were generally elevated by indomethacin, suggesting inhibition of the DNA synthesis by an endogenously produced cyclooxygenase product(s). Consistent with this suggestion, exogenous prostaglandin E2 suppressed cytokine induced DNA synthesis. All of the cytokines studied might play a role in the synovial hyperplasia present in rheumatoid disease.
authors.affiliation: University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Australia.
authors.forename: D M
authors.initials: DM
authors.lastname: Butler
authors.forename: D S
authors.initials: DS
authors.lastname: Piccoli
authors.forename: P H
authors.initials: PH
authors.lastname: Hart
authors.forename: J A
authors.initials: JA
authors.lastname: Hamilton
mesh_terms: D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D015232:Dinoprostone / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology*; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D015232:Dinoprostone