EphA2 receptor signaling mediates inflammatory responses in lipopolysaccharide-induced lung injury

Ji Young Hong, Mi Hwa Shin, Kyung Soo Chung, Eun Young Kim, Ji Ye Jung, Young Ae Kang, Young Sam Kim, Se Kyu Kim, Joon Chang, Moo Suk Park

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13 Citations (Scopus)

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±2.93 vs. 11.45±1.20, respectively; p=0.004). Cell counts (EphA2 mAb+LPS: 11.33×104±8.84×104 vs. IgG+LPS: 208.0×104±122.6×104; p=0.018) and total protein concentrations (EphA2 mAb+LPS: 0.52±0.41 mg/mL vs. IgG+LPS: 1.38±1.08 mg/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 110γ, phospho-Akt, nuclear factor κB, 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.

Original languageEnglish
Pages (from-to)218-226
Number of pages9
JournalTuberculosis and Respiratory Diseases
Volume78
Issue number3
DOIs
Publication statusPublished - 2015 Jul

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Infectious Diseases

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    Hong, J. Y., Shin, M. H., Chung, K. S., Kim, E. Y., Jung, J. Y., Kang, Y. A., Kim, Y. S., Kim, S. K., Chang, J., & Park, M. S. (2015). EphA2 receptor signaling mediates inflammatory responses in lipopolysaccharide-induced lung injury. Tuberculosis and Respiratory Diseases, 78(3), 218-226. https://doi.org/10.4046/trd.2015.78.3.218