title: Ischemic postconditioning downregulates Egr-1 expression and attenuates postischemic pulmonary inflammatory cytokine release and tissue injury in rats.
abstract: BACKGROUND
  The early growth response-1 (Egr-1) gene is upregulated after an ischemia-reperfusion (IR) challenge and upregulates target genes, such as proinflammatory cytokines. Ischemic postconditioning (IPostC) attenuates lung IR injury and reduces the systemic inflammatory response by activating heme oxygenase-1 (HO-1). However, the role of Egr-1 in IPostC protection against lung IR injury and inflammation and its interplay with HO-1 in IPostC protection is unknown.
  
  
  METHODS
  Sprague-Dawley rats or cultured A549 cells were subjected to IR or hypoxia/reoxygenation with or without IPostC or hypoxic postconditioning in the presence or absence of Egr-1 inhibition using Egr-1 antisense oligodeoxyrinonucleotide or Egr-1 small interfering RNA transfection. Lung injury was assessed by measuring the lung wet/dry weight ratio, histologic change, and malondialdehyde content. The amount of lactate dehydrogenase release in culture medium was detected to evaluate cell injury. The protein expression of Egr-1, interleukin (IL)-1β, and HO-1 was assessed by Western blot.
  
  
  RESULTS
  Inhibition of Egr-1 significantly attenuated lung IR injury and the inflammation response caused by IR or hypoxia/reoxygenation, as shown by the alleviated lung pathologic changes, decreased pulmonary malondialdehyde content, wet/dry ratio, reduced release of the cytokines tumor necrosis factor-α, IL-6, and IL-8 in the bronchoalveolar lavage, and reduced Egr-1, IL-1β, and HO-1 protein expression and HO-1 activity. IPostC or hypoxic postconditioning reduced the postischemic Egr-1 expression and conferred similar protection against lung IR injury as Egr-1 inhibition.
  
  
  CONCLUSIONS
  Egr-1 plays an important role in regulating the HO-1 production induced by IR or hypoxia/reoxygenation. Thus, downregulation of Egr-1 expression might represent one of the major mechanisms whereby IPostC confers protection against pulmonary IR insult.
authors.affiliation: Department of Cardiothoracic Surgery, Fifth Affiliated Hospital of Zunyi Medical College, Zhuhai, China.
authors.forename: Huozhi
authors.initials: H
authors.lastname: Wu
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Lei
authors.forename: Jiang
authors.initials: J
authors.lastname: Yuan
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Dayong
authors.initials: D
authors.lastname: Zhang
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Gu
authors.forename: Liangqing
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D057775:Ischemic Postconditioning; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D008315:Malondialdehyde; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat