To characterize the effects of interleukin-la (IL-1) on prostanoid biosynthesis by human rheumatoid synovium microvessel endothelium (HSE).
Methods. HSE cells were treated with cytokines, metabolic inhibitors, and steroids under various conditions, and prostaglandin biosynthesis was determined by radioimmunoassay. Newly synthesized cyclooxygenase (COX) was quantitated by immunoprecipitation of metabolically labeled HSE cell lysates. The effects of IL-1 on levels of messenger RNA (mRNA) for COX I1 were also determined.
Results. IL-1 induced an increase in COX activity (as assessed by prostaglandin E, release) that was doseand time-dependent and was blocked by cycloheximide, actinomycin D, and dexamethasone. IL-1 induced a selective increase in COX I1 mRNA and biosynthesis of COX I1 protein that was blocked by dexamethasone.
Conclusion. IL-1 treatment of HSE cells induces COX 11, as demonstrated by both Northern blotting and immunoprecipitation. The induction of COX I1 expression provides, at least in part, a mechanism for the pronounced increase in prostanoid synthesis observed in HSE cells following incubation with IL-1. The selective up-regulation of HSE COX I1 by inflammatory cytokines such as IL-1 suggests that development of specific pharmaceutical inhibitors for this novel isozyme may