Cross-talk between group IIA-phospholipase A2 and inducible NO-synthase in rat renal mesangial cells.
Features of glomerulonephritis are expression of the inducible form of NO synthase (iNOS) as well as expression of the secretory group IIA-phospholipase A2 (sPLA2) in mesangial cells. Interleukin 1beta (IL-1beta) induces both enzymes with a similar time course resulting in an increase in nitrite production and sPLA2-IIA activity. In this study we investigated the relationship between the formation of NO and sPLA2-IIA induction in rat renal mesangial cells. Incubation of mesangial cells with the NO-donor, spermine-NONOate, for 24 h induced sPLA2-IIA mRNA expression and activity, whereas S-nitroso glutathione alone had only a small stimulatory effect. Stimulation of cells with IL-1beta caused a marked increase in sPLA2-IIA mRNA and activity that were potentiated 3 fold by both NO donors. Coincubation of cells with IL-1beta and the NOS inhibitor, L-N(G) monomethylarginine (L-NMMA), caused a dose-dependent inhibition of cytokine-induced sPLA2-IIA mRNA expression and activity. sPLA2-IIA activity was not stimulated by 8-bromo-cyclic GMP indicating that NO-induced sPLA2-IIA induction is independent of cyclic GMP-mediated signal transduction. These data show that NO contributes to the expression by cytokines of sPLA2-IIA and establishes a novel type of interaction between iNOS and sPLA2-IIA in mesangial cells. This cross-talk between inflammatory mediators may help to promote and sustain an inflammatory state in the kidney.
Rupprecht
G
G
Klinikum der Johann-Wolfgang-Goethe-Universität, Medizinische Klink IV, Funktionsbereich Nephrologie, Frankfurt am Main, Germany.
Scholz
K
K
Beck
K F
KF
Geiger
H
H
Pfeilschifter
J
J
Kaszkin
M
M
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000201:enzymology*; D007375:Interleukin-1 / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010741:Phospholipases A / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D013268:Stimulation, Chemical; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D020030:Nitric Oxide Donors; D009573:Nitrites; D015124:8-Bromo Cyclic Adenosine Monophosphate; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D010741:Phospholipases A