Endogenous glucocorticoids inhibit myocardial inflammation induced by lipopolysaccharide: involvement of regulation of histone deacetylation
Journal of Cardiovascular Pharmacology, Zhang HN et al.
These findings indicate that endogenous glucocorticoids (GCs) are able to inhibit myocardial inflammation induced by LPS. Endogenous GCs represent an important endogenous anti–inflammatory mechanism for myocardium in rats and such mechanism injury may be an important factor for pathogenesis of cardiac diseases.
The potential role of endogenous glucocorticoids (GCs) in regulation of myocardial inflammation was investigated.
Authors showed that reduction of endogenous GCs level by adrenalectomy promoted the production of basal and LPS–induced pro–inflammatory cytokines, which could be partly reversed by supplementing with exogenous physiological level of hydrocortisone.
Inhibition of GCs–glucocorticoid receptor (GR) signaling pathway with GR antagonist mifepristone (RU486) or histone deacetylase (HDAC) inhibitor trichostatin A (TSA) also increased the levels of basal and LPS–induced pro–inflammatory cytokines.
Moreover, blockade of GC–GR signaling pathway by adrenalectomy, RU486 or TSA enhanced LPS–induced myocardial NF– κB activation and histone acetylation, but inhibited myocardial HDAC expression and activity.
Cardiac function studies demonstrated that blockade of GC–GR signaling pathway aggravated inflammation–induced cardiac dysfunction.
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