Emerging evidence indicates that myocardial
inflammation plays a key role in the pathogenesis of
cardiac diseases. But the exact mechanisms for this chronic inflammatory disorder have not been elucidated.
Glucocorticoids (GCs) are the most effective anti-inflammatory treatments available for many inflammatory diseases. However, it is unknown whether endogenous GCs are able to exert anti-inflammatory effect on myocardial
inflammation. In this study, the potential role of endogenous GCs in the regulation of myocardial
inflammation was investigated. We showed that the reduction of endogenous GC level by
adrenalectomy promoted the production of basal and
lipopolysaccharide (LPS)-induced proinflammatory
cytokines, which could be partly reversed by supplementing with exogenous physiological level of
hydrocortisone. Inhibition of GC receptor (GR) signaling pathway with GR antagonist
mifepristone (
RU486) or
histone deacetylase inhibitor trichostatin A (
TSA) also increased the levels of basal and LPS-induced proinflammatory
cytokines. Moreover, blockade of GC-GR signaling pathway by
adrenalectomy,
RU486 or
TSA enhanced LPS-induced myocardial nuclear factor-κB activation and
histone acetylation but inhibited myocardial
histone deacetylase expression and activity. Cardiac function studies demonstrated that blockade of the GC-GR signaling pathway aggravated
inflammation-induced cardiac dysfunction. These findings indicate that endogenous 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.