Expression and regulation of cyclooxygenase-2 in rat microglia.
Increased levels of prostanoids have been implicated in various neuropathological diseases, although little is known about their cellular sources inside the brain. In this study, we analyzed the expression of cyclooxygenase-2 (COX-2), a key enzyme in arachidonic acid metabolism, in rat microglia. COX-2 mRNA and protein as well as prostaglandin E2 formation were almost undetectable in unstimulated microglial cultures but were found to be strongly upregulated in response to lipopolysaccharide. However, in contrast to most peripheral cells, proinflammatory cytokines such as tumor necrosis factor alpha, interleukin-1 beta or interleukin-6 failed to markedly induce COX-2 expression. Similar effects were observed by analyzing transcription nuclear factor-kappa B (NF-kappa B) which was strongly activated in microglia by lipopolysaccharide but not by incubation with cytokines. Moreover, known inhibitors of NF-kappa B activation, such as dexamethasone and the antioxidant pyrrolidine dithiocarbamate, as well as the protein kinase C (PKC) inhibitor Gö6976, strongly reduced lipopolysaccharide-induced COX-2 transcription, indicating the involvement of NF-kappa B and PKC in COX-2 expression. Our results suggest that microglia may represent an important source of prostanoids in the brain, thus reinforcing their prominent role in cerebral inflammatory processes.
Bauer
M K
MK
Department of Psychiatry and Psychotherapy, Albert-Ludwigs-University of Freiburg, Germany.
Lieb
K
K
Schulze-Osthoff
K
K
Berger
M
M
Gebicke-Haerter
P J
PJ
Bauer
J
J
Fiebich
B L
BL
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002540:Cerebral Cortex; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000201:enzymology* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D016207:Cytokines; D007527:Isoenzymes; D008070:Lipopolysaccharides; D011453:Prostaglandins; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases