Inhibition of Ca2+-independent phospholipase A2 by bromoenol lactone attenuates prostaglandin generation induced by interleukin-1 beta 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 A2 (sPLA2). In the present study, we investigated the possible involvement of Ca2+-independent phospholipase A2 (iPLA2) in the generation. The results showed that bromoenol lactone, a relatively selective iPLA2 inhibitor, significantly attenuated prostaglandin E2 generation induced by interleukin-1beta and dibutyryl cAMP in parallel with the inhibition of iPLA2 activity. However, the inhibitor did not affect sPLA2 release upon stimulation, activities of sPLA2 or cytosolic phospholipase A2, or Ca2+ ionophore-induced arachidonic acid liberation. These results suggest that prostaglandin E2 generation upon stimulation may be partially mediated by iPLA2 in addition to sPLA2.
Akiba
S
S
Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Japan. akiba@mb.kyoto-phu.ac.jp
Hayama
M
M
Sato
T
T
D000818:Animals; D003994:Bucladesine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054467:Phospholipases A2; D011453:Prostaglandins / Q000096:biosynthesis*; D011753:Pyrones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007375:Interleukin-1; D009281:Naphthalenes; D010726:Phosphodiesterase Inhibitors; D011453:Prostaglandins; D011753:Pyrones; D003994:Bucladesine; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium