Resveratrol Ameliorates LPS-induced Acute Lung Injury Mouse Model via Induction of Tristetraprolin

Abstract

Aim: In this study, we aimed to investigate whether resveratrol has anti-inflammatory effects on LPS-induced ALI via TTP enhancement. Background: Acute lung injury (ALI) is a syndrome of diffuse infammatory lung injury with increased pulmonary edema and the rapid onset of hypoxemic respiratory failure. Resveratrol is a stilbenoid, a form of natural phenol, and a phytoalexin produced by a variety of plants in reaction to injury or when they are attacked by pathogens like bacteria or fungi. Resveratrol exhibits a potent antiinflammatory effect in LPS-induced ALI, while the underlying mechanisms remain elusive. Objective: Tristetraprolin (TTP) is a RNA binding protein that is an important endogenous inhibitor of inflammation. The objective of the present study is to investigate whether resveratrol has anti- inflammatory effects on LPS-induced ALI via TTP enhancement. Methods: Forty male C57BL/6 mice were randomly assigned to four groups and intratracheally instilled with 5 mg/kg lipopolysaccharide (LPS) to induce ALI. Results: LPS-induced lung pathological damage, lung edema, and neutrophil infiltration were reduced by resveratrol pretreatment. Furthermore, resveratrol inhibited the LPS-induced rise in TNF- α, IL-1β and IL-6 levels in BAL fluids. In the LPS-challenged mouse's lung tissue, resveratrol clearly boosted sirtuin1 (SIRT1) and TTP protein expression, while also increasing TTP expression while reducing proinflammatory cytokines. EX527, on the other hand, reversed resveratrol's effects. Conclusion: According to our findings, resveratrol attenuated pulmonary inflammation and lung injury in mice with LPS‑induced ALI， at least partly correlated with promoting the activation of SIRT1/TTP signaling pathway, highlighting these pathways as potential targets for intervention in LPS -induced lung injury.