Abstract
Cultured rat synovial cells generate PGE2 upon stimulation with a factor derived from rate polymorphonuclear cells (Prostaglandins 27, 697, 1984). E-5110 inhibited PGE2 generation by the synovial cells. The IC50 values (microM) for inhibition of PGE2 generation were 0.026 for E-5110, 0.008 for indomethacin, 0.112 for piroxicam, 0.003 for R-830, 0.667 for BW-755C and 2.05 for benoxaprofen. Calcium ionophore A-23187-stimulated LTB4 generation by human neutrophils was inhibited by E-5110 with an IC50 value of 0.20 microM, which was similar to NDGA. The inhibition of LTB4 by E-5110 was more potent than that of R-830, BW-755C or benoxaprofen. E-5110 also inhibited superoxide generation by human neutrophils stimulated with opsonized zymosan, f-Met-Leu-Phe and phorbol myristate acetate. These results indicate that E-5110 is a potent dual inhibitor that suppresses superoxide generation.
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