Hydrogen sulfide attenuates lipopolysaccharide-induced inflammation by inhibition of p38 mitogen-activated protein kinase in microglia

The present study attempts to investigate the effect of H2S 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 H2S donor, 10-300 mu mol/L) attenuated LPS-stimulated nitric oxide (NO) in a concentration dependent manner. Stimulating endogenous H2S production decreased LPS-stimulated NO production, whereas lowering endogenous H2S level increased basal NO production. Western blot analysis showed that both exogenous and endogenous H2S 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 mu mol/L) and SB 203580 (1 mu mol/L) significantly attenuated LPS-induced tumor necrosis factor-a secretion, another inflammatory indicator. In addition, NaHS (10-300 mu mol/L) dose-dependently decreased LPS-stimulated NO production in primary cultured astrocytes, suggesting that the anti-neuroinflammatory effect of H2S is not specific to microglial cells alone. Taken together, H2S 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.