CONTRIBUTION OF GROUP-II PHOSPHOLIPASE A(2) TO ARACHIDONIC-ACID RELEASE AND PROSTAGLANDIN SYNTHESIS BY MESANGIAL CELLS

Interleukin 1 (IL-1) and tumour necrosis factor (TNF)alpha have been f ound to increase group II phospholipase A(2) (PLA(2)) synthesis and se cretion by mesangial cells. In all cases 85%-90% of the enzyme is secr eted from the cells and a parallel increase in prostaglandin (PGE(2)) synthesis is observed. We report here that co-incubation with a monocl onal antibody that specifically binds and neutralizes rat group II PLA (2) attenuates IL-1 beta and TNF alpha-stimulated PGE(2) production by 45% and 52%, respectively. CGP43182, a specific inhibitor of group II PLA(2), potently blocks IL-1 beta- and TNF alpha-stimulated PGE(2) sy nthesis in intact mesangial cells with 1C(50)s of 1.3 and 1.0 mu M, re spectively. alpha (TNF alpha) stimulate sPLA(2) activity and prostagla ndin (PG) production in several cell systems including mesangial cells [3]. Recently it was shown that cytokines, such as IL-1 beta, TNF alp ha or transforming growth factor beta(2) also enhance cPLA(2) activity [4]. The precise functions of sPLA(2) and cPLA(2) and especially the contributions of both enzymes to eicosanoid synthesis under physiologi cal and pathological conditions are not known. In this report we have addressed the relative contribution of sPLA(2) to IL-1 beta- and TNF a lpha-stimulated PGE(2) synthesis in rat mesangial cells.