Key result
Physiological concentrations of hydrocortisone inhibited LPS-induced TNF-α and IL-1β production in cardiac fibroblasts, an effect that required HDAC2 and was impaired by oxidative stress.
p-value: p=<0.05
Physiological concentrations of glucocorticoids inhibit LPS-induced inflammation in cardiac fibroblasts via an HDAC2-dependent mechanism, which is impaired by oxidative stress.
Oxidative stress may blunt glucocorticoid anti-inflammation in cardiac fibroblasts via HDAC2; leaves open human relevance and therapeutic targeting.
We previously suggested that endogenous glucocorticoids (GCs) may inhibit myocardial inflammation induced by lipopolysaccharide (LPS) in vivo. However, the possible cellular and molecular mechanisms were poorly understood. In this study, we investigated the role of physiological concentration of GCs in inflammation induced by LPS in cardiac fibroblasts and explored the possible mechanisms. The results showed that hydrocortisone at the dose of 127 ng/mL (equivalent to endogenous basal level of GCs) inhibited LPS (100 ng/mL)-induced productions of TNF-α and IL-1β in cardiac fibroblasts. Xanthine oxidase/xanthine (XO/X) system impaired the anti-inflammatory action of GCs through downregulating HDAC2 activity and expression. Knockdown of HDAC2 restrained the anti-inflammatory effects of physiological level of hydrocortisone, and blunted the ability of XO/X system to downregulate the inhibitory action of physiological level of hydrocortisone on cytokines. These results suggested that HDAC2 was required by the physiological concentration of GC to inhibit inflammatory response. The dysfunction of HDAC2 induced by oxidative stress might be account for GC resistance and chronic inflammatory disorders during the cardiac diseases.
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Zhang et al. (2017) studied Myocardial inflammation (preclinical model). Hydrocortisone vs. LPS alone or XO/X system was evaluated on TNF-α and IL-1β production and HDAC2 activity/expression (p=<0.05). Physiological concentrations of hydrocortisone inhibited LPS-induced TNF-α and IL-1β production in cardiac fibroblasts, an effect that required HDAC2 and was impaired by oxidative stress.
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