Inhibition of Ca2+-independent phospholipase A2 by bromoenol lactone attenuates prostaglandin generation induced by interleukin-1β and dibutyryl cAMP in rat mesangial cells

Cytokine-induced prostaglandin generation in rat mesangial cells has been suggested to be dependent on the expression of secretory phospholipase A(2) (sPLA(2)). In the present study, we investigated the possible involvement of Ca2+-independent phospholipase A(2) (iPLA(2)) in the generation. The results showed that bromoenol lactone, a relatively selective iPLA(2) inhibitor, significantly attenuated prostaglandin E-2 generation induced by interleukin-1 beta and dibutyryl cAMP in parallel with the inhibition of iPLA2 activity, However, the inhibitor did not affect sPLA2 release upon stimulation, activities of sPLA(2) or cytosolic phospholipase A(2), or Ca2+ ionophore-induced arachidonic acid liberation, These results suggest that prostaglandin E-2 generation upon stimulation may be partially mediated by iPLA(2) in addition to sPLA(2). (C) 1998 Federation of European Biochemical Societies.