Phospholipase A2 inhibitors p-bromophenacyl bromide and arachidonyl trifluoromethyl ketone suppressed interleukin-2 (IL-2) expression in murine primary splenocytes.
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 microM BPB and 10 microM 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 microM BPB and 20 microM AACOCF3. 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.
Ouyang
Y
Y
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824, USA.
Kaminski
N E
NE
D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007375:Interleukin-1 / Q000235:genetics*; D051379:Mice; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D000098:Acetophenones; D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D012333:RNA, Messenger; C081565:arachidonyltrifluoromethane; D010741:Phospholipases A; D054467:Phospholipases A2; C006821:4-bromophenacyl bromide