title: Propofol inhibits lipopolysaccharide-induced lung epithelial cell injury by reducing hypoxia-inducible factor-1alpha expression.
abstract: BACKGROUND
  Lipopolysaccharide (LPS) may activate hypoxia-inducible factor (HIF)-1α, which up-regulates cytokine expression and the lethality of LPS-induced shock. We investigated the effect of propofol on HIF-1α 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-1α 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-1α 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-1α, interleukin (IL)-6, keratinocyte-derived chemokine, and tumour necrosis factor-alpha (TNF-α) in the lungs of endotoxaemic mice. In HIF-1α knockdown-A549 cells, LPS-induced TNF-α, IL-6, and the pro-apoptotic gene, BNIP3 expression and apoptosis were reduced. Propofol, but not an inhibitor of nuclear factor κB, reduced HIF-1α expression in LPS-stimulated A549 cells. Propofol also down-regulated, in A549 cells, the expression of IL-6, IL-8, and TNF-α, 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-1α, BNIP3, and cytokine production. Using propofol to inhibit HIF-1α expression may protect against the acute lung injury caused by LPS-induced sepsis.
authors.affiliation: Institute of Medical Science, College of Health Science, Chang Jung Christian University, Tainan, Taiwan.
authors.forename: C-H
authors.initials: CH
authors.lastname: Yeh
authors.forename: W
authors.initials: W
authors.lastname: Cho
authors.forename: E C
authors.initials: EC
authors.lastname: So
authors.forename: C-C
authors.initials: CC
authors.lastname: Chu
authors.forename: M-C
authors.initials: MC
authors.lastname: Lin
authors.forename: J-J
authors.initials: JJ
authors.lastname: Wang
authors.forename: C-H
authors.initials: CH
authors.lastname: Hsing
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D018686:Anesthetics, Intravenous / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D004847:Epithelial Cells / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015742:Propofol / Q000494:pharmacology* / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D018686:Anesthetics, Intravenous; D016207:Cytokines; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008070:Lipopolysaccharides; D015742:Propofol