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 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 micro mol/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 micro mol/L) and SB 203580 (1 micro mol/L) significantly attenuated LPS-induced tumor necrosis factor-alpha secretion, another inflammatory indicator. In addition, NaHS (10-300 micro mol/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.
Hu
Li-Fang
LF
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Wong
Peter T-H
PT
Moore
Philip K
PK
Bian
Jin-Song
JS
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008070:Lipopolysaccharides; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D006862:Hydrogen Sulfide