Mechanism of stimulation of prostaglandin synthesis by a factor from rheumatoid synovial tissue.

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Abstract
Rheumatoid synovial cell monolayers, with [1-14C]arachidonic acid ([1-14C]AA) incorporated into cell lipids, are stimulated by a factor (RSF) produced by explant cultures of rheumatoid synovial tissue to produce up to 50-fold increases in [1-14C]prostaglandin[PG]E2 and [1-14C]PGI2. Levels of free [1-14C]AA released from RSF-stimulated cells are generally lower than [1-14C]AA levels in cultures of untreated cells. These observations are inconsistent with a mechanism of PG stimulation consisting of an increase in phospholipase activity, because this mechanism would increase free AA levels as well as PG. A mechanism is proposed in which free AA is maintained at low steady-state levels by reacylation of free AA into phospholipids at a rate more rapid than its reaction with cyclooxygenase to form PG. In this mechanism, stimulation of the rate of the cyclooxygenase step by RSF accounts for increased PG synthesis and the decreased release of AA. This mechanism may also be applicable to the stimulation of PG synthesis by several other agents. Preliminary characterization of the RSF indicates that it is a protein, and molecular sieve chromatography indicates that its MW is .apprx. 18,000. The production of RSF by rheumatoid synovial tissue is suppressed to undetectable levels by 1 .mu.M dexamethasone.

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