Wortmannin enhances lipopolysaccharide-induced inducible nitric oxide synthase expression in microglia in the presence of astrocytes in rats.
Microglia, the primary inflammatory cells in the brain, are activated upon brain injury. Activated microglia produce nitric oxide (NO), a major toxin to neuronal cells. It has been reported that astrocytes inhibit microglial activation. In this study, we found that wortmannin, a natural inhibitor of phosphatidylinositol 3-kinase, significantly increased lipopolysaccharide (LPS)-induced NO release and inducible nitric oxide synthase (iNOS) expression in microglia in the presence but not in the absence of astrocytes. In response to LPS even in the presence of wortmannin, iNOS immunoreactivity was detected in microglia but not in astrocytes. These results suggest that astrocytes could regulate microglia-mediated brain inflammation by inhibiting microglial NO release/iNOS expression via a wortmannin-sensitive mechanism.
Pyo
Hankyoung
H
Department of Pharmacology, Ajou University School of Medicine, Suwon, Kyunggi-do, 442-721, South Korea.
Yang
Myung-Soon
MS
Jou
Ilo
I
Joe
Eun-hye
EH
D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D015151:Immunoblotting; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012477:Salmonella enteritidis; D000077191:Wortmannin
D000730:Androstadienes; D008070:Lipopolysaccharides; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000077191:Wortmannin