Inhibition by lysophosphatidylcholine of nitric oxide production in interleukin 1 beta-stimulated vascular smooth muscle cells.
In vascular smooth muscle cells (VSMC), inflammatory cytokines such as interleukin 1 beta(IL-1 beta) stimulated nitric oxide (NO) production via the expression of an inducible type of NO synthase (iNOS). Lysophosphatidylcholine (LPC) is a major phospholipid component of atherogenic oxidized low density lipoprotein (Ox-LDL). In this study, we examined the effect of LPC on IL-1 beta-stimulated NO production in cultured. VSMC. LPC by itself did not stimulate the production of nitrite, a stable metabolite of NO, but dose-dependently inhibited IL-1 beta-stimulated nitrite production. LPC inhibited IL-1 beta-stimulated iNOS protein expression, whereas LPC did not inhibit IL-1 beta-stimulated iNOS mRNA expression. Analysis of iNOS protein degradation rate revealed that LPC had no effect on degradation rate of iNOS protein, suggesting that LPC inhibited iNOS translation. Moreover, Ox-LDL inhibited IL-1 beta-stimulated NO production by inhibiting iNOS protein expression without affecting iNOS mRNA expression. These results indicate that Ox-LDL negatively modulates IL-1 beta-induced NO production through the action of LPC, probably by blocking translation of iNOS mRNA.
Okamoto
Y
Y
Department of Internal Medicine, Kobe University School of Medicine.
Kawahara
Y
Y
Yokoyama
M
M
D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002478:Cells, Cultured / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*
D008244:Lysophosphatidylcholines; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase