Resveratrol decreases CD45+ CD206- subtype macrophages in LPS-induced murine acute lung injury by SOCS3 signalling pathway

Abstract

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) are life-threatening condition in critically ill patients. Resveratrol (Res), a natural polyphenol, has therapeutic effect in animal model with ALI; however, whether Res attenuates ALI through modulation of macrophage phenotypes in the animal model remains unknown. We in this study treated LPS-induced murine ALI with 30 mg/kg Res and observed significantly reduced severity of ALI in the Res-treated mice 48 hours after Res treatment. Neutrophil infiltrates were significantly reduced, accompanied with lower infiltration of CD45⁺ Siglec F^- phenotype macrophages, but higher population of CD45⁺ Siglec F⁺ and CD45⁺ CD206⁺ alternatively activated macrophages (M2 cells) in the Res-treated mice with ALI. In addition, the expression of IL-1beta and CXCL15 cytokines was suppressed in the treated mice. However, Res treatment in mice with myeloid cell-restricted SOCS3 deficiency did not significantly attenuate ALI severity and failed to increase population of both CD45⁺ Siglec F⁺ and CD45⁺ CD206⁺ M2 subtype macrophages in the murine ALI. Further studies in wild-type macrophages revealed that Res treatment effectively reduced the expression of IL-6 and CXCL15, and increased the expression of arginase-1, SIRT1 and SOCS3. However, macrophages' lack of SOCS3 expression were resistant to the Res-induced suppression of IL-6 and CXCL15 in vitro. Thus, we conclude that Res suppressed CD45⁺ Siglec F^- and CD45⁺ CD206^- M1 subtype macrophages through SOCS3 signalling in the LPS-induced murine ALI.

Keywords: SOCS3; acute lung injury; macrophages; resveratrol.