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Hydrogen sulfide attenuates lipopolysaccharide‐induced inflammation by inhibition of p38 mitogen‐activated protein kinase in microglia
Author(s) -
Hu LiFang,
Wong Peter T.H.,
Moore Philip K.,
Bian JinSong
Publication year - 2007
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 - 10.1111/j.1471-4159.2006.04283.x
Subject(s) - sodium hydrosulfide , microglia , p38 mitogen activated protein kinases , nitric oxide synthase , nitric oxide , lipopolysaccharide , chemistry , mapk/erk pathway , protein kinase a , neuroinflammation , endogeny , tumor necrosis factor alpha , inflammation , kinase , endocrinology , microbiology and biotechnology , medicine , biology , biochemistry , immunology , hydrogen sulfide , sulfur , organic chemistry
The present study attempts to investigate the effect of H 2 S on lipopolysaccharide (LPS)‐induced inflammation in both primary cultured microglia and immortalized murine BV‐2 microglial cells. We found that exogenous application of sodium hydrosulfide (NaHS) (a H 2 S donor, 10–300 μmol/L) attenuated LPS‐stimulated nitric oxide (NO) in a concentration‐dependent manner. Stimulating endogenous H 2 S production decreased LPS‐stimulated NO production, whereas lowering endogenous H 2 S level increased basal NO production. Western blot analysis showed that both exogenous and endogenous H 2 S significantly attenuated the stimulatory effect of LPS on inducible nitric oxide synthase expression, which is mimicked by SB 203580, a specific p38 mitogen‐activated protein kinase (MAPK) inhibitor. Exogenously applied NaHS significantly attenuated LPS‐induced p38 MAPK phosphorylation in BV‐2 microglial cells. Moreover, both NaHS (300 μmol/L) and SB 203580 (1 μmol/L) significantly attenuated LPS‐induced tumor necrosis factor‐α secretion, another inflammatory indicator. In addition, NaHS (10–300 μmol/L) dose‐dependently decreased LPS‐stimulated NO production in primary cultured astrocytes, suggesting that the anti‐neuroinflammatory effect of H 2 S is not specific to microglial cells alone. Taken together, H 2 S produced an anti‐inflammatory effect in LPS‐stimulated microglia and astrocytes, which may be due to inhibition of inducible nitric oxide synthase and p38 MAPK signaling pathways. These findings may have important implications in the treatment of neuroinflammation‐related diseases.