Effect of 1,25-dihydroxyvitamin D3 on interleukin 1 beta actions and cell growth in human synovial fibroblast cultures.

Abstract

To investigate the effects of vitamin D3 [1,25-(OH)2D3] metabolites on interleukin 1 beta (IL-1 beta) stimulated secretory activities and on the proliferation of human synovial fibroblasts in culture. Dose dependent effects on IL-1 beta actions were determined in nonproliferating cultures containing 1% fetal calf serum (FCS) in the culture medium. Production of prostaglandin E (PGE), collagenase and hyaluronic acid (HA) was measured respectively by radioimmunoassay, enzymatic degradation of radiolabelled collagen gels after collagenase activation and 14C-glucosamine incorporation. Effects on cell growth in 10% FCS were monitored colorimetrically, by staining cells with crystal violet. 1,25-(OH)2D3 inhibited the effects of IL-1 beta on PGE production by up to 90%, with half maximal inhibition at 2.0 x 10(-10) M. Inhibitory effects on stimulated collagenase and HA production and cell growth were also found but were less marked. At 10(-7) M 1,25-(OH)2D3 inhibition was 50, 21 and 50%, respectively. 24,25-dihydroxyvitamin D3 was a less potent inhibitor than 1,25-(OH)2D3. Neither metabolite influenced IL-1 beta effects on PGE or sulfated glycosaminoglycan production in human articular cartilage in tissue culture. Our results suggest that the active metabolites of vitamin D3 may modulate the behavior of synovial fibroblasts in articular inflammatory processes.