Protective effect of resveratrol against acute lung injury induced by lipopolysaccharide via inhibiting the myd88-dependent Toll-like receptor 4 signaling pathway

Abstract

Resveratrol, a polyphenol mainly present in grapes and red wine, demonstrated varied pharmacological activities. The protective effects of resveratrol on acute lung injury (ALI) induced by lipopolysaccharide (LPS) have remained elusive. The present study investigated whether the protective effect of resveratrol on ALI induced by LPS was via inhibiting the myeloid differentiation primary response gene (myd88)‑dependent toll‑like receptor (TLR)4 signaling pathway. Mice were pretreated with 5 or 45 mg/kg resveratrol for three days prior to bronchial perfusion with 25 mg/kg LPS. At 12 h after surgery, the ratio of the wet to the dry (w/d) lung was calculated to assess tissue edema. Histological changes of the lungs were detected using hematoxylin and eosin staining and the protein expression levels of TLR4, myd88 and nuclear factor kappa‑light‑chain‑enhancer of activated B cells (NF‑κB) were measured by western blot analysis. The concentration of interleukin (IL)‑6 and cyclooxygenase (COX)‑2 in the bronchoalveolar lavage fluid were detected by ELISA. The results showed that resveratrol can suppress the edema, inflammatory cell infiltration and alveolar structure damage of lungs in mice with ALI and decrease the lung w/d ratio. Additionally, resveratrol markedly decreased the expression of TLR4, myd88 and NF‑κB and decreased the concentration of inflammatory cytokines, including IL‑6 and COX‑2. Therefore, it can be concluded that resveratrol has a protective effect against ALI induced by LPS, at least in part by inhibiting the myd88‑dependent TLR4 signaling pathway. In conclusion, resveratrol pretreatment has a protective effect against LPS‑induced ALI in mice, which indicates that resveratrol may serve as a potential therapeutic agent for treating ALI in the clinic.