Glucocorticoids differentially regulate the innate immune responses of TLR4 and the cytosolic DNA sensing pathway

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Glucocorticoids (GCs) are widely used to treat the chronic inflammatory disorders because of their powerful anti-inflammatory properties; however, their effects on macrophage-mediated immune responses are not completely understood. In the present study, we found that GCs decreased LPS-mediated TBK1 activation and the expression of IFN-β, RANTES and CXCL-10; however, poly(dA:dT)-induced TBK1 activity and cytokine expression were not affected by GCs treatment. Furthermore, GCs decreased the expression of key autophagy-related genes (ATGs), including ATG5, ATG7 and ATG12, and inhibited autophagy in macrophages after LPS stimulation. However, GCs had no effect on poly(dA:dT)-mediated autophagy and ATG expression in macrophages. Collectively, this study demonstrates that GCs inhibit the TLR4-mediated innate immune response, but do not affect the cytosolic DNA sensing pathway. This provides new insights into the immunomodulatory mechanisms of GCs in macrophages, which may provide useful information for the clinical use of GCs in treating chronic inflammatory disorders.HighlightsGCs decreased LPS-mediated TBK1 activation and cytokines expression.GCs had no effects on TBK1 activity and cytokines expression induced by poly(dA:dT).GCs decreased ATGs expression and inhibited autophagy in Mφ upon LPS stimulation.GCs did not affect poly(dA:dT)-mediated autophagy and ATGs expression in Mφ.

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