摘要
目的探讨生理浓度下糖皮质激素对脂多糖(lipopo-lysaccharide,LPS)诱导大鼠肺泡上皮细胞IL-6表达的影响及其机制。方法LPS、生理浓度的氢化可的松、过氧化氢等处理细胞,ELISA测定细胞上清IL-6水平,并对细胞组蛋白去乙酰化酶(histone deacetylase,HDAC)的活性进行测定。结果与对照组相比LPS明显诱导细胞IL-6的蛋白表达(P<0·01)。生理浓度氢化可的松明显降低LPS诱导的IL-6蛋白水平表达的作用(P<0·01)。HDAC抑制剂(Trichosta-tin,TSA)明显拮抗氢化可的松的这种作用(P<0·01);与对照相比,LPS明显下调HDAC的活性(P<0·01),糖皮质激素抑制LPS下调HDAC活性的作用(P<0·01);过氧化氢增强LPS诱导IL-6蛋白表达的作用(P<0·01),过氧化氢、LPS和氢化可的松共同处理细胞后,其IL-6的浓度较LPS与H2O2共同刺激组差别无统计学意义(P>0·05)。过氧化氢浓度依赖性地降低细胞HDAC活性(P<0·01)。结论生理浓度的糖皮质激素同样具有抗炎作用,氧化应激可抑制糖皮质激素抗炎作用,具体机制可能与其降低HDAC活性有关,这些机制可能在与氧化应激有关的呼吸系统疾病中发挥重要作用。
Aim To investigate the role of physiological concentration of glucocorticoids on the inflammation mediator IL-6 expression in response to LPS in rat alveolar epithelial cells(CCL149).Methods The CCL149 were treated with LPS,H2O2 and glucocorticoid respectively.Flammtory mediator IL-6 protein expression was measured with ELISA,and the activity of histone deacetylase(HDAC) was measured using colorimetric HDAC activity assay kit.Results IL-6 protein levels were increased in cells exposed to 10 mg·L-1 LPS.Hydrocortisone decreased IL-6 protein expression induced by LPS.Such effect of hydrocortisone was blunt by HDAC inhibitor trichostatinA treatment(10 μg·L-1).LPS decreased HDAC activity.Hydrocortisone increased HDAC activity.The expression of IL-6 protein induced by LPS was further enhanced by H2O2 treatment.Pretreatment with H2O2 resulted in the inhibition of antiflammtion effect of glucocorticoids.Conclusion Physiological concentration of glucocorticoids could suppress inflammatory response,and this effects requires recruitment of HDAC.Oxidants such as H2O2 may cause the failure of glucocorticoids to function effectively,and the reason may be related to the reduction of HDAC activity.This mechanism may contribute to the pathogenesis of pulmonary disorder.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2007年第8期1073-1076,共4页
Chinese Pharmacological Bulletin
基金
广东省自然科学基金团队项目资助(No05200239)
关键词
糖皮质激素
炎症
氧化应激
glucocorticoid
inflammation
oxidative stress
