Article: Ischemic postconditioning downregulates Egr-1 expression and attenuates postischemic pulmonary inflammatory cytokine release and tissue injury in rats
| Title | Ischemic postconditioning downregulates Egr-1 expression and attenuates postischemic pulmonary inflammatory cytokine release and tissue injury in rats |
|---|---|
| Authors | Wu, H Lei, S Yuan, J Liu, X Zhang, D Gu, X Zhang, L Xia, Z |
| Keywords | Egr-1 Heme oxygenase 1 Ischemic postconditioning Lung ischemia reperfusion |
| Issue Date | 2013 |
| Publisher | Elsevier Inc.. The Journal's web site is located at http://www.elsevier.com/locate/jsre |
| Citation | Journal of Surgical Research, 2013, v. 181 n. 2, p. 204-212 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.jss.2012.07.031 |
| 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. MATERIALS AND 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)-1beta, 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-alpha, IL-6, and IL-8 in the bronchoalveolar lavage, and reduced Egr-1, IL-1beta, 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. |
| ISSN | 0022-4804 2011 Impact Factor: 2.247 2011 SCImago Journal Rankings: 0.162 |
| DOI | http://dx.doi.org/10.1016/j.jss.2012.07.031 |
| dc.contributor.author | Wu, H |
|---|---|
| dc.contributor.author | Lei, S |
| dc.contributor.author | Yuan, J |
| dc.contributor.author | Liu, X |
| dc.contributor.author | Zhang, D |
| dc.contributor.author | Gu, X |
| dc.contributor.author | Zhang, L |
| dc.contributor.author | Xia, Z |
| dc.date.accessioned | 2012-09-20T07:50:52Z |
| dc.date.available | 2012-09-20T07:50:52Z |
| dc.date.issued | 2013 |
| dc.description.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. MATERIALS AND 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)-1beta, 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-alpha, IL-6, and IL-8 in the bronchoalveolar lavage, and reduced Egr-1, IL-1beta, 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. |
| dc.description.nature | Link_to_subscribed_fulltext |
| dc.identifier.citation | Journal of Surgical Research, 2013, v. 181 n. 2, p. 204-212 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.jss.2012.07.031 |
| dc.identifier.doi | http://dx.doi.org/10.1016/j.jss.2012.07.031 |
| dc.identifier.hkuros | 209806 |
| dc.identifier.issn | 0022-4804 2011 Impact Factor: 2.247 2011 SCImago Journal Rankings: 0.162 |
| dc.identifier.pmid | 22878149 |
| dc.identifier.scopus | eid_2-s2.0-84876408681 |
| dc.identifier.uri | http://hdl.handle.net/10722/163750 |
| dc.language | eng |
| dc.publisher | Elsevier Inc.. The Journal's web site is located at http://www.elsevier.com/locate/jsre |
| dc.publisher.place | United States |
| dc.relation.ispartof | Journal of Surgical Research |
| dc.subject | Egr-1 |
| dc.subject | Heme oxygenase 1 |
| dc.subject | Ischemic postconditioning |
| dc.subject | Lung ischemia reperfusion |
| dc.title | Ischemic postconditioning downregulates Egr-1 expression and attenuates postischemic pulmonary inflammatory cytokine release and tissue injury in rats |
| dc.type | Article |