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

Phospholipase A(2) (PLA(2)) has been postulated to play a role in the regul ation of cytokine expression. Therefore, the objective of the present study was to investigate the effects of PLA(2) inhibitors p-bromophenacyl bromid e (BPB) and arachidonyl trifluoromethyl ketone (AACOCF(3)) on interleukin-2 (IL-2) expression in murine primary splenocytes. Pretreatment of the splen ocytes with both BPB and AACOCF(3) suppressed phorbol 12-myristate 13-aceta te plus ionomycin-induced IL-2 secretion in a concentration-dependent manne r. Inhibition > 90% of IL-2 secretion was observed at 1 mu M BPB and 10 mu M AACOCF(3) compared to the respective vehicle control. Likewise, IL-2 stea dy-state mRNA expression was inhibited by both PLA(2) inhibitors in a conce ntration-dependent fashion with > 90% inhibition at 1 mu M BPB and 20 mu M AACOCF(3). Taken together, these data demonstrated that PLA(2) inhibitors B PB and AACOCF(3) 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 PLA(2) may have marked effects on T- cell function.