Polyunsaturated fatty acids potentiate interleukin-1-stimulated arachidonic acid release by cells overexpressing type IIA secretory phospholipase A 2

Abstract

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 secretory PLA 2 (sPLA 2-IIA)-mediated arachidonic acid (AA) release from interleukin-1 (IL-1)-stimulated cells. When 293 cells prelabeled with [ 3H]AA were incubated with exogenous PUFAs in the presence of IL-1 and serum, there was a significant increase in [ 3H]AA release (in 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 Ca 2+-independent PLA 2, overexpression. Transfection of cPLA 2 into sPLA 2-IIA-expressing cells produced a synergistic increase in IL-1-dependent [ 3H]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 hydrolysis by sPLA 2-IIA.