Resveratrol upregulates SOCS1 production by lipopolysaccharide-stimulated RAW264.7 macrophages by inhibiting miR-155

Resveratrol is a polyphenolic compound extracted from grapes and the Chinese herb, Polygonum cuspidatum. In the present study, in order to elucidate the molecular mechanisms of action of resveratrol in host immune cells, we examined the effects of resveratrol on the inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. The cells were treated with resveratrol prior to stimulation with LPS (1 mu g/ml). Resveratrol downregulated the expression of inflammatory markers, such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, induced by LPS, and inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and signal transducer and activator of transcription (STAT)1/STAT3. Resveratrol also upregulated the production of suppressor of cytokine signaling 1 (SOCS1; a STAT inhibitor) and suppressed the expression of miR-155, which plays an essential role in the innate and adaptive immune response. Given the elevated levels of SOCS1 in LPS-induced inflammation, our results suggest that resveratrol exerts anti-inflammatory effects due to the upregulation of SOCS1, which is a potential target of miR-155, as well as of miR-155 mimics and inhibitors. These findings suggest the benefits of resveratrol, which are derived from its regulation of SOCS1 expression via the inhibition of miR-155, and indicate that resveratrol may be developed as a useful agent for the treatment of inflammatory diseases.