Human recombinant interleukin-1 beta stimulates glycosaminoglycan production in human synovial fibroblast cultures.
Human recombinant interleukin-1 beta (rIL-1 beta) stimulated glycosaminoglycan (GAG) production in human synovial fibroblast cultures. A dose-dependent increase in GAG production was found, to a maximum of 500%. Increase was detected at doses as low as 1 pg/ml of rIL-1 beta, reached a maximum at 10-100 pg/ml, and was apparent 10 hours after addition of rIL-1 beta. Stimulation of GAG was always accompanied by increased accumulation of prostaglandin E (PGE) in culture media and by increased collagenase production in approximately one-half the experiments. Indomethacin (5 micrograms/ml) completely inhibited PGE stimulation by rIL-1 beta, but only partially inhibited that of GAG overproduction and had no effect on collagenase production. Hydrocortisone (2 micrograms/ml) inhibited stimulation of all 3 parameters. Stimulation of hyaluronate in synovial cultures prevailed over that of sulfated GAG, which occurred to a lesser extent. Our results support earlier suggestions that interleukin-1 is a major active mononuclear cell factor that is capable of inducing profound changes in connective tissue cell function.
D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000502:physiology*; D003012:Microbial Collagenase / Q000096:biosynthesis; D011458:Prostaglandins E / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013583:Synovial Membrane / Q000378:metabolism*
D006025:Glycosaminoglycans; D007375:Interleukin-1; D011458:Prostaglandins E; D011994:Recombinant Proteins; D003609:Dactinomycin; D003513:Cycloheximide; D003012:Microbial Collagenase; D006854:Hydrocortisone; D007213:Indomethacin