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.

Calreticulin Blockade Attenuates Murine Acute Lung Injury by Inducing Polarization of M2 Subtype Macrophages

“…Our previous study showed that Siglec F+ subtype macrophages were decreased in the mice with ALI, but that was reversed by administration of anti-oxidant resveratrol, indicating a useful new biomarker of M2 macrophage, that was similar to CD206 (8). Consistent with the previous results, we in this study also observed significantly more population of anti-inflammatory Siglec F+CD206+ M2 subtype macrophages in the aCALR-treated mice with ALI.…”

“…A body of evidences showed that macrophages can be modulated by many reagents (4)(5)(6)(7). Our previous research revealed that antioxidant resveratrol can attenuate ALI through polarization of alternatively activated macrophage or M2 cells (8). The therapeutic effects were associated with STAT3/SOCS3 signaling pathway.…”

Modulation of adipocyte size and fat pad weight via resveratrol releasing scaffolds implanted into the epididymal adipose tissue

“…Therefore, we believe that macrophages are a particularly interesting population for further study as they are recruited to the implant site 38 and fuse together to form multinucleated giant cells that are in direct contact with the scaffold 46 . Resveratrol has extensively been shown to polarize macrophages to an anti‐inflammatory phenotype 32,58–60 . Interestingly, anti‐inflammatory macrophages use fatty acid oxidation as their key energy source compared to proinflammatory macrophages that use glucose metabolism.…”

Herbal Active Ingredients: Potential for the Prevention and Treatment of Acute Lung Injury

“…It exhibits protective effects in various ALI models. In a LPS-mediated ALI model, resveratrol can counteract lung inflammation by suppressing CD45 + Siglec F − and CD45 + CD206 − M1 subtype macrophages [ 76 ]. In a sepsis-induced ALI model, resveratrol can suppress the production of proinflammatory cytokines and the apoptosis of alveolar macrophages through the activation of the vascular endothelial growth factor-B (VEGF-B) pathway, thereby exhibiting anti-inflammatory and antiapoptotic effects [ 77 ].…”