期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 88, 期 7, 页码 1577-1594出版社
WILEY
DOI: 10.1002/jnr.22319
关键词
amoeboid microglia; COX-2; mPGES-1; NF-kappa B; proinflammatory mediators
资金
- National University of Singapore [R-181-000-086-592, R-181-000-065-112]
Microglia express cyclooxygenase-2 (COX-2) and microsomal prostaglandin-E synthase (mPGES-1) but their localization in the amoeboid microglial cells (AMC), considered to be the nascent brain macrophages, in the developing brain has remained unexplored; furthermore, their interrelation and regulation have also remained to be fully elucidated. We show here that AMC in postnatal rat brain constitutively expressed COX-2 and mPGES-1 whose immunoexpression was upregulated in rats given lipopolysaccharide (LPS) injections. Reverse transcriptase-polymerase chain reaction and Western blot analysis of the callosal tissue rich in AMC revealed that COX-2 and mPGES-1 mRNA and protein expression was augmented following LPS injections. BV-2 cells also exhibited COX-2 and mPGES-1 expression which was enhanced by LPS. However, in cells treated with LPS coupled with COX-2 neutralization, the mRNA expression levels of COX-2, mPGES-1, tumor necrosis factor-alpha, interleukin-1 beta and inducible nitric oxide synthase were significantly suppressed; production of prostaglandin E-2 and reactive oxygen species also decreased. Western blot analysis confirmed the changes of protein levels of the above mediators. Remarkably, COX-2 neutralization concomitantly suppressed the protein expression levels of nuclear factor-kappa B (NF-kappa B), phos-NF-kappa B and phos-I kappa B-alpha as well as translocation of NF-kappa B as determined by flow cytometry. In conclusion, AMC in the developing brain expressed COX-2 and mPGES-1 notably when stimulated by LPS. It is suggested that this may be involved in local inflammation during development. Our results have further shown that COX-2 neutralization may be effective in suppressing production of inflammatory mediators and hence its potential use in alleviating neuroinflammation. (C) 2009 Wiley-Liss, Inc.
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