Propofol Affects H/R Induced Alveolar Macrophage Death via TLR4/NF-κB/NLRP3 Signaling Pathway

Abstract

Acute lung injury (ALI) is one of the most common acute and critical diseases in clinic. The main pathological features of ALI are increase of pulmonary Vascular permeability, accumulation of inflammatory cells and pulmonary dysfunction due to diffuse pulmonary edema. At present, it is generally believed that the main pathogenesis of ALI is the uncontrolled inflammatory response in the lung. It has been found that cell death plays an important role in the regulation of inflammatory reaction in acute lung injury. Propofol, a new fast-acting, short-acting intravenous anesthetic, it is known that ALI can be alleviated by inhibiting the release of inflammatory factors and inhibiting the anoxia/reoxygenation-induced autophagy, chemotaxis and oxidative stress in macrophages, however, the mechanism of its role in the death of alveolar macrophage remains unknown. Therefore, the aim of this study was to investigate the role of propofol in alveolar macrophage death and its mechanism through anoxia-reoxygenation induced ALI. NR8383 was alveolar macrophage as anoxia-reoxygenation model. LDH release, CCK-8, Elisa and Western Blot were used to investigate the pathway of propofol through TLR4/NF-κB/NLRP3 signaling pathway, mechanism of inhibition of hypoxia-reoxygenation induced alveolar macrophage death of NR8383. The results showed that propofol decreased the release of LDH and the content of IL-1β and IL-18. In addition, propofol pretreatment reduced the protein expression levels of TLR4 downstream pathways (p65 phosphorylation, NLRP3, cleaved-caspase-1, and GSDMD-N), all of which could be reversed by TLR4 receptor antagonist and NLRP3 receptor inhibitors, it’s causing a decrease in alveolar macrophage activity. The results showed that propofol could significantly reduce anoxia-reoxygenation-induced alveolar macrophage death. Propofol may modulate alveolar macrophage death through TLR4/NF-κB/NLRP3 inflammatory signaling pathway, thereby alleviating anoxia-reoxygenation induced Ali, suggesting that propofol may be a potential drug for the treatment of Ali.