Dehydroepiandrosterone inhibits lipopolysaccharide-induced nitric oxide production in BV-2 microglia

Citation
Mj. Wang et al., Dehydroepiandrosterone inhibits lipopolysaccharide-induced nitric oxide production in BV-2 microglia, J NEUROCHEM, 77(3), 2001, pp. 830-838
Citations number
62
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROCHEMISTRY
ISSN journal
0022-3042 → ACNP
Volume
77
Issue
3
Year of publication
2001
Pages
830 - 838
Database
ISI
SICI code
0022-3042(200105)77:3<830:DILNOP>2.0.ZU;2-6
Abstract
Levels of dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEAS) decline during aging and reach even lower levels in Alzheimer's disease (A D). DHEA is known to exhibit a variety of functional activities in the CNS, including an increase of memory and learning, neurotrophic and neuroprotec tive effects, and the reduction of risk of age-related neurodegenerative di sorders. However, the influence of DHEA on the immune functions of glial ce lls is poorly understood. In this study, we investigated the effect of DHEA on activated glia. The production of inducible nitric oxide synthase (iNOS ) was studied in lipopolysaccharide (LPS)stimulated BV-2 microglia, as a mo del of glial activation. The results showed that DHEA but not DHEAS signifi cantly inhibited the production of nitrite in the LPS-stimulated BV-2 cell cultures. Pretreatment of BV-2 cells with DHEA reduced the LPS-induced iNOS mRNA and protein levels in a dose-dependent manner. The LPS-induced iNOS a ctivity in BV-2 cells was decreased by the exposure of 100 muM DHEA. Moreov er, DHEA suppressed iNOS gene expression in LPS-stimulated BV-2 cells did n ot require de novo synthesis of new proteins or destabilize of iNOS mRNA. S ince DHEA is biosynthesized by astrocytes and neurons, our findings suggest that it might have an important regulatory function on microglia.