Abstract
The effect of misoprostol on interleukin-1beta (IL-1beta)-mediated phospholipid metabolism, arachidonic acid release, and prostaglandin E(2) (PGE(2)) production was examined using normal skin fibroblasts and synovial fibroblasts from patients with osteoarthritis. We found that both IL-1beta and misoprostol induced arachidonic acid release, suggesting enhanced phospholipase A(2) activation. Both Il-1beta and IL-1beta/misoprostol, but not misoprostol alone, induced a significant increase in PGE(2) levels compared with controls. Even though PGE(2) production was not significantly increased by misoprostol alone, misoprostol synergistically enhanced IL-1beta-mediated cyclooxygenase activity (sixfold to eightfold) and PGE(2) synthesis in normal fibroblasts but not in OA synovial fibroblasts. Additionally, misoprostol dramatically affected the arachidonate-labeling of triglyceride and cholesterol ester pools; the significance of this is as yet unclear. Together, the results suggest that misoprostol may upregulate the conversion of arachidonic acid to PGE(2) by enhancing the IL-1beta-induced activation/synthesis of cyclooxygenase.
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