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Dehydroepiandrosterone inhibits lipopolysaccharide‐induced nitric oxide production in BV‐2 microglia
Author(s) -
Wang MeiJen,
Huang HsuehMeei,
Chen HuanLian,
Kuo JonSon,
Jeng KeeChing G.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00295.x
Subject(s) - dehydroepiandrosterone , nitric oxide , microglia , endocrinology , lipopolysaccharide , nitric oxide synthase , neuroprotection , medicine , neuroactive steroid , neuroinflammation , astrocyte , neurotrophic factors , chemistry , biology , inflammation , central nervous system , receptor , androgen , hormone , gabaa receptor
Levels of dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEAS) decline during aging and reach even lower levels in Alzheimer's disease (AD). DHEA is known to exhibit a variety of functional activities in the CNS, including an increase of memory and learning, neurotrophic and neuroprotective effects, and the reduction of risk of age‐related neurodegenerative disorders. However, the influence of DHEA on the immune functions of glial cells 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 model of glial activation. The results showed that DHEA but not DHEAS significantly 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 activity in BV‐2 cells was decreased by the exposure of 100 µ m DHEA. Moreover, DHEA suppressed iNOS gene expression in LPS‐stimulated BV‐2 cells did not require de novo synthesis of new proteins or destabilize of iNOS mRNA. Since DHEA is biosynthesized by astrocytes and neurons, our findings suggest that it might have an important regulatory function on microglia.