STRUCTURAL CORRELATIONS OF PHORBOL-ESTER-INDUCED STIMULATION OF PGE2 PRODUCTION BY HUMAN RHEUMATOID SYNOVIAL-CELLS

Eight phorbol esters were studied for their ability to stimulate prostaglandin [PGE2] production in human rheumatoid synovial cells over the dose range 0.1 ng to 1.0 .mu.g. These derivatives were based upon phorbol, 4-deoxyphorbol and 12-deoxyphorbol nuclei. This activity was structurally dependent and, although it did not correlated with the actions of the same compounds to induce erythema in vivo, it did correlate with their ability to stimulate human lymphocyte mitogenesis. Stimulation of PGE2 production by a phorbol and a 12-deoxyphorbol analog was inhibited in this system by indomethacin and dexamethasone.