Inhibition of physiological concentration of glucocorticoids on LPS-induced inflammation in rat alveolar epithelial cells / 中国药理学通报

ABSTRACT

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 ?g?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.