Polyunsaturated fatty acids potentiate interleukin-1-stimulated arachidonic acid release by cells overexpressing type IIA secretory phospholipase A2

By analyzing human embryonic kidney 293 cell transfectants stably overexpressing various types of phospholipase A(2) (PLA(2)), we have shown that polyunsaturated fatty acids (PUFAs) preferentially activate type IIA secretor) PLA(2) (sPLA(2)-IIA)-mediated arachidonic acid (AA) release from interleukin-1 (TL-1)-stimulated cells. When 293 cells prelabeled with [H-3]AA mere incubated with exogenous PUFAs in the presence of IL-1 and serum, there was a significant increase in [H-3]AA release tin the order AA > linoleic acid > oleic acid), which was augmented markedly by sPLA(2)-IIA and modestly by type IV cytosolic PLA(2) (cPLA(2)), but only minimally by type VI Ca2+-independent PLA(2), overexpression. Transfection of cPLA2 into sPLA(2)-IIS-expressing cells produced a synergistic increase in IL-1-dependent [H-3]AA release and subsequent prostaglandin production. Our results support the proposal that prior production of AA by cPLA(2) in cytokine-stimulated cells destabilizes the cellular membranes, thereby rendering them more susceptible to subsequent hgdrolysis by sPLA(2)-IIA. (C) 1999 Federation of European Biochemical Societies.