Rheumatoid synovial cell hormone responses modulated by cell-cell interactions.

Abstract

Cellular interactions within the rheumatoid synovium are likely to be responsible for the destructive properties of this tissue. The responses to hormones which regulate connective tissue metabolism may also be influenced by these cell-cell interactions. To determine the effect of cellular interactions on responses to hormones, human peripheral blood mononuclear cells were cocultured with adherent rheumatoid synovial cells. Coculture resulted in a decrease in response to prostaglandin E2 as assessed by a reduction in the magnitude of the acute prostaglandin-induced cyclic AMP response. In contrast, coculture resulted in an increase in the magnitude of the acute parathyroid hormone-induced cyclic AMP response. The decrease in response to prostaglandin was reversed by the presence of indomethacin during the preincubation, whereas indomethacin had no effect on the cyclic AMP response to parathyroid hormone. Increases in endogenous synovial cell prostaglandin production (stimulated by soluble factors released by the mononuclear cells) accounted for the subsequent decrease in the response to exogenous prostaglandin. The increase in cyclic AMP response to parathyroid hormone could not be explained by a soluble factor and was independent of ambient prostaglandin levels.