Propofol inhibits lipopolysaccharide-induced lung epithelial cell injury by reducing hypoxia-inducible factor-1α expression

Background. Lipopolysaccharide (LPS) may activate hypoxia-inducible factor (HIF)-1 alpha, which up-regulates cytokine expression and the lethality of LPS-induced shock. We investigated the effect of propofol on HIF-1 alpha expression and acute lung injury in LPS-treated mice. Methods. A series of both positive and negative control experiments were performed. We injected BALB/C mice with propofol or vehicle i.p. immediately and 12 h after an LPS challenge. After 24 h, we examined the lung wet/dry weight ratio, neutrophil infiltration, and HIF-1 alpha mRNA expression and inflammatory cytokines in the lung tissue. Survival was determined for 48 h after LPS injection. In vitro, we determined the responses of A549 cells, with and without HIF-1 alpha silenced, to treatment with LPS alone and LPS plus propofol. Results. Propofol prolonged survival and attenuated acute lung injury and decreased the expression of HIF-1 alpha, interleukin (IL)-6, keratinocyte-derived chemokine, and tumour necrosis factor-alpha (TNF-alpha) in the lungs of endotoxaemic mice. In HIF-1 alpha knockdown-A549 cells, LPS-induced TNF-alpha, IL-6, and the pro-apoptotic gene, BNIP3 expression and apoptosis were reduced. Propofol, but not an inhibitor of nuclear factor kappa B, reduced HIF-1 alpha expression in LPS-stimulated A549 cells. Propofol also down-regulated, in A549 cells, the expression of IL-6, IL-8, and TNF-alpha, Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), and apoptosis. Conclusions. Propofol reduces apoptosis in LPS-stimulated lung epithelial cells by decreasing HIF-1 alpha, BNIP3, and cytokine production. Using propofol to inhibit HIF-1 alpha expression may protect against the acute lung injury caused by LPS-induced sepsis.