Aspirin modulates LPS-induced nitric oxide release in rat glial cells.
Nitric oxide and prostaglandins are among the numerous substances released by activated glial cells. The aim of this study was to evaluate the effect of high-level aspirin on iNOS expression in cultured rat glial cells treated with lipopolysaccharide (LPS) as pathological stimulator. Using Western Blotting, we verified that aspirin enhanced LPS-induced iNOS expression and the presence of 15-deoxy-Delta(12,14)-prostaglandin (15d-PGJ2) suppressed this aspirin effect. However, the exposure of LPS-treated glial cells to aspirin resulted in a decrease of NO production. These results suggest that aspirin interferes with the cross-talk of prostaglandins and NO, blocking the endogenous negative control exerted by COX products on iNOS expression. On the other side, aspirin seems to act directly on iNOS reducing its activity, even if it does not completely block NO release by LPS-stimulated glial cells. Then aspirin could maintain homeostatic functions of NO, while it prevents toxic effects, corresponding to high NO concentrations.
Marchini
C
C
Department of Molecular, Cellular and Animal Biology, University of Camerino, Via Scalzino 1, 62032 Camerino, Italy.
Angeletti
M
M
Eleuteri
A M
AM
Fedeli
A
A
Fioretti
E
E
D000818:Animals; D000831:Animals, Newborn; D001241:Aspirin / Q000008:administration & dosage*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D015230:Prostaglandin D2 / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D051381:Rats; D017208:Rats, Wistar
C477819:15-deoxyprostaglandin J2; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001241:Aspirin; D015230:Prostaglandin D2