PMID: 7526844Oct 15, 1994Paper

Possible role of protein kinase C-epsilon isoenzyme in inhibition of interleukin 1 beta induction of nitric oxide synthase in rat renal mesangial cells

The Biochemical Journal
H Mühl, J Pfeilschifter

Abstract

In cultured glomerular mesangial cells, interleukin 1 beta (IL-1 beta) has been shown to induce a dose- and time-dependent accumulation of nitrite, a stable metabolite of nitric oxide (NO). In parallel, increased levels of mRNA of an inducible macrophage-type of nitric oxide synthase (iNOS) were observed after incubating mesangial cells with IL-1 beta. Here we report that addition of the biologically active phorbol esters, phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDBu), dose-dependently inhibited the IL-1 beta-stimulated increase in iNOS mRNA levels and nitrite production. In contrast, the biologically inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate, had no effect on cytokine induction of iNOS and nitrite formation. Incubation of mesangial cells with PMA or PDBu alone, in the absence of IL-1 beta, did not trigger any iNOS expression. Time-course studies indicated that phorbol ester needs to be added for only 1 h in order to maximally inhibit cytokine-induced nitrite production. Down-regulation of protein kinase C (PKC)-alpha and -delta isoenzymes by 8 h PMA or PDBu treatment before stimulation with IL-1 beta still resulted in full inhibition of iNOS induction. In contrast, a 24 h treatment of...Continue Reading

Citations

Jul 30, 2014·Journal of Pharmacological Sciences·Daisuke MoriMasatoshi Hori
Oct 6, 2005·Journal of the Society for Gynecologic Investigation·Boonrit ThongsongPuttur D Prasad
Dec 13, 2003·Biological Chemistry·Hartmut KleinertUlrich Förstermann
May 21, 2013·American Journal of Physiology. Lung Cellular and Molecular Physiology·Émilie BoncoeurYves Berthiaume
Aug 5, 1998·The American Journal of Physiology·M G MohauptE Schulze-Lohoff
May 30, 2015·Molecular Cancer Research : MCR·Alvaro Gutierrez-UzquizaMarcelo G Kazanietz
Aug 29, 1997·Biochimica Et Biophysica Acta·H SekiM H Sullivan
Jan 1, 1996·Life Sciences·J L Bankers-FulbrightD J McKean

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