Hydrogen sulfide attenuates lipopolysaccharide-induced inflammation by inhibition of p38 mitogen-activated protein kinase in microglia
Hydrogen sulfide attenuates lipopolysaccharide-induced inflammation by inhibition of p38 mitogen-activated protein kinase in microglia
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DOI：
10.1111/j.1471-4159.2006.04283.x
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发表时间：
2007-02-01
影响因子：
4.7
通讯作者：
Bian, Jin-Song
中科院分区：
文献类型：
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作者：
Hu, Li-Fang;Wong, Peter T. -H.;Bian, Jin-Song
本研究试图探讨硫化氢对脂多糖（LPS）诱导的炎症在原代培养的小胶质细胞和永生化的小鼠BV-2小胶质细胞的影响。我们发现，外源性应用硫氢化钠（NaHS）（H2S供体，10-300 μ mol/L）以浓度依赖性方式减弱LPS刺激的一氧化氮（NO）。刺激内源性H2S的产生减少LPS刺激的NO产生，而降低内源性H2S水平增加基础NO产生。Western blot分析表明，外源性和内源性H2S显着减弱LPS对诱导型一氧化氮合酶表达的刺激作用，这是模仿SB 203580，一个特定的p38丝裂原活化蛋白激酶（MAPK）抑制剂。外源性NaHS显著减弱BV-2小胶质细胞中LPS诱导的p38 MAPK磷酸化。此外，NaHS（300 μ mol/L）和SB 203580（1 μ mol/L）均显著减弱LPS诱导的肿瘤坏死因子-α分泌（另一种炎症指标）。此外，NaHS（10-300 μ mol/L）剂量依赖性地降低LPS刺激的原代培养星形胶质细胞中NO的产生，这表明H2S的抗神经炎症作用不是仅针对小胶质细胞的。总之，H2S在LPS刺激的小胶质细胞和星形胶质细胞中产生抗炎作用，这可能是由于抑制诱导型一氧化氮合酶和p38 MAPK信号通路。这些发现可能对神经炎症相关疾病的治疗具有重要意义。
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.