Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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EphA2 Receptor Signaling Mediates Inflammatory Responses in Lipopolysaccharide-Induced Lung Injury

  • Hong, Ji Young (Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Shin, Mi Hwa (Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Chung, Kyung Soo (Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Kim, Eun Young (Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Jung, Ji Ye (Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Kang, Young Ae (Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Kim, Young Sam (Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Kim, Se Kyu (Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Chang, Joon (Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Park, Moo Suk (Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine)
  • Received : 2014.12.16
  • Accepted : 2015.04.27
  • Published : 2015.04.30
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Abstract

Background: Eph receptors and ephrin ligands have several functions including angiogenesis, cell migration, axon guidance, fluid homeostasis, oncogenesis, inflammation and injury repair. The EphA2 receptor potentially mediates the regulation of vascular permeability and inflammation in response to lung injury. Methods: Mice were divided into 3 experimental groups to study the role of EphA2 signaling in the lipopolysaccharide (LPS)-induced lung injury model i.e., IgG+phosphate-buffered saline (PBS) group (IgG instillation before PBS exposure), IgG+LPS group (IgG instillation before LPS exposure) and EphA2 monoclonal antibody (mAb)+LPS group (EphA2 mAb pretreatment before LPS exposure). Results: EphA2 and ephrinA1 were upregulated in LPS-induced lung injury. The lung injury score of the EphA2 mAb+LPS group was lower than that of the IgG+LPS group ($4.30{\pm}2.93$ vs. $11.45{\pm}1.20$, respectively; p=0.004). Cell counts (EphA2 mAb+LPS: $11.33{\times}10^4{\pm}8.84{\times}10^4$ vs. IgG+LPS: $208.0{\times}10^4{\pm}122.6{\times}10^4$; p=0.018) and total protein concentrations (EphA2 mAb+LPS: $0.52{\pm}0.41mg/mL$ vs. IgG+LPS: $1.38{\pm}1.08mg/mL$; p=0.192) were decreased in EphA2 mAb+LPS group, as compared to the IgG+LPS group. In addition, EphA2 antagonism reduced the expression of phospho-p85, phosphoinositide 3-kinase $110{\gamma}$, phospho-Akt, nuclear factor ${\kappa}B$, and proinflammatory cytokines. Conclusion: This results of the study indicated a role for EphA2-ephrinA1 signaling in the pathogenesis of LPS-induced lung injury. Furthermore, EphA2 antagonism inhibits the phosphoinositide 3-kinase-Akt pathway and attenuates inflammation.

Keywords

References

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