SIRT1 ameliorated septic associated-lung injury and macrophages apoptosis via inhibiting endoplasmic reticulum stress

Abstract

BackgroundThe inappropriate apoptosis of macrophages plays an important role in the pathogenesis of sepsis-induced acute lung injury, however, the detailed regulatory mechanisms remain largely unknown. As an endogenous apoptosis pathway, endoplasmic reticulum (ER) stress plays an important role in cell damage in patients with sepsis. Clarifying the ER stress response and its effect on macrophages during the development of sepsis is helpful to explore new strategies for the prevention and treatment of ALI in sepsis. MethodsThe mouse model and the RAW264.7 inflammation model were stimulated with LPS to establish in vivo and in vitro. We explored the effects of different expression levels of silent information regulator factor 2-related enzyme 1 (SIRT1) on the ER stress response and apoptosis of macrophages in the sepsis-related injury model. ResultsOur studies found that the increased expression of SIRT1 can significantly improve sepsis-related lung injury and relieve lung inflammation. SRT1720, a SIRT1 activator, can significantly inhibit the ER stress response of lung tissue and macrophages, inhibit the expression of pro-apoptotic proteins, promote the expression of anti-apoptotic proteins, and reduce macrophages of apoptosis. While the EX527, an inhibitor of SIRT1, had the opposite effect. ConclusionSIRT1 can significantly improve sepsis-associated lung injury and LPS-induced macrophage apoptosis. This protective effect is closely related to its inhibition of the ER stress response via the PERK/eIF2-α/ATF4/CHOP pathway.