Heme oxygenase-1 mediates the anti-inflammatory effect of isoflurane preconditioning in LPS-stimulated macrophages

• 来源期刊: 中国药理学报(英文版)
• 关键词: anesthesia lipopolysaccharide heme oxygenase inflammation
• 年，卷（期）: 2009,（2）
• 页码范围: 228-234
• 页数: 7页
• 语种: 英文
• DOI: 10.1038/aps.2008.19

摘要

Aim:The aim of this study was to investigate the anti-inflammatory action of isoflurane preconditioning in a model of lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages and examine the role of heine oxygenase (HO)-1 in this process.Methods: Murine 264.7 macrophages were pretreated with or without 1%-3% isoflurane for 1 h.Thirty minutes later,the cells were incubated with or without LPS for 24 h.Cell viability was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell injury was assessed by measuring the release of lactate dehydrogenase (LDH).HO-1 and inducible nitric oxide synthase (iNOS) protein expression was analyzed by Western blotting.Tumor necrosis fac-tor (TNF)-α levels,nitrite production and HO activity were also determined.Results: Pretreatment with the nontoxic and clinically approved anesthetic isoflurane potently attenuated the cell injury and the decrease in cell viability that was induced by LPS.Treatment or pretreatrnent with 2% isoflurane induced HO-1 protein expression and caused an induction of HO activity.This result correlated with a decrease in iNOS expression,a decrease in the production of nitric oxide (NO) and impaired release of TNF-α in LPS-stimulated macrophages.Blockade of HO activ-ity with tin protoporphyrin (SnPP) reversed these effects.Conclusion: Isoflurane preconditioning exerts its anti-inflammatory activity through the HO-1 pathway in an in vitro inflammation model.