Phospholipase A2 inhibitors p-bromophenacyl bromide and arachidonyl trifluoromethyl ketone suppressed interleukin-2 (IL-2) expression in murine primary splenocytes

Abstract

Phospholipase A₂ (PLA₂) has been postulated to play a role in the regulation of cytokine expression. Therefore, the objective of the present study was to investigate the effects of PLA₂ inhibitors p-bromophenacyl bromide (BPB) and arachidonyl trifluoromethyl ketone (AACOCF₃) on interleukin-2 (IL-2) expression in murine primary splenocytes. Pretreatment of the splenocytes with both BPB and AACOCF₃ suppressed phorbol 12-myristate 13-acetate plus ionomycin-induced IL-2 secretion in a concentration-dependent manner. Inhibition >90% of IL-2 secretion was observed at 1 μM BPB and 10 μM AACOCF₃ compared to the respective vehicle control. Likewise, IL-2 steady-state mRNA expression was inhibited by both PLA₂ inhibitors in a concentration-dependent fashion with >90% inhibition at 1 μM BPB and 20 μM AACOCF_3. Taken together, these data demonstrated that PLA₂ inhibitors BPB and AACOCF₃ are robust inhibitors of IL-2 expression at both the mRNA and protein levels in murine splenocytes. Moreover, these findings suggest that drugs and chemicals which inhibit PLA₂ may have marked effects on T-cell function.