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EphA2 Receptor Signaling Mediates Inflammatory Responses in Lipopolysaccharide-Induced Lung Injury.

Hong JY, Shin MH, Chung KS, Kim EY, Jung JY, Kang YA, Kim YS, Kim SK, Chang J, Park MS - Tuberc Respir Dis (Seoul) (2015)

Bottom Line: 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.Furthermore, EphA2 antagonism inhibits the phosphoinositide 3-kinase-Akt pathway and attenuates inflammation.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

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: 11.33×10(4)±8.84×10(4) vs. IgG+LPS: 208.0×10(4)±122.6×10(4); 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.

No MeSH data available.


Related in: MedlinePlus

The effects of ephrinA1-mediated activation of EphA2 on the phosphoinositide 3-kinase (PI3K)/Akt signaling pathways in lipopolysaccharide (LPS)-induced lung injury. EphA2-ephrinA1 signaling may contribute to the development of LPS-induced lung injury. Exposure to LPS resulted in activation of the EphA2-ephrinA1 and PI3K/Akt/nuclear factor κB (NF-κB) signaling pathway. EphA2 monoclonal antibody-induced inhibition of EphA2 signaling resulted in decreased PI3K/Akt/NF-κB-dependent inflammatory processes. These results suggested crosstalk between EphA2 signaling and PI3K/Akt/NF-κB signaling in LPS-induced lung injury. TNF-α: tumor necrosis factor α; IL: interleukin.
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Figure 7: The effects of ephrinA1-mediated activation of EphA2 on the phosphoinositide 3-kinase (PI3K)/Akt signaling pathways in lipopolysaccharide (LPS)-induced lung injury. EphA2-ephrinA1 signaling may contribute to the development of LPS-induced lung injury. Exposure to LPS resulted in activation of the EphA2-ephrinA1 and PI3K/Akt/nuclear factor κB (NF-κB) signaling pathway. EphA2 monoclonal antibody-induced inhibition of EphA2 signaling resulted in decreased PI3K/Akt/NF-κB-dependent inflammatory processes. These results suggested crosstalk between EphA2 signaling and PI3K/Akt/NF-κB signaling in LPS-induced lung injury. TNF-α: tumor necrosis factor α; IL: interleukin.

Mentions: EphrinA1-dependent EphA2 activation may be an unrecognized contributor to LPS-induced lung injury. Antagonizing EphA2 not only resulted in diminished expression of the PI3Kγ isoform, but it also led to decreased NF-κB activation and expression of proinflammatory cytokines through the PI3K-Akt pathway. Crosstalk of EphA2 signaling with the PI3K-Akt pathway may contribute to the neutrophil-driven inflammatory process in LPS-induced lung injury (Figure 7).


EphA2 Receptor Signaling Mediates Inflammatory Responses in Lipopolysaccharide-Induced Lung Injury.

Hong JY, Shin MH, Chung KS, Kim EY, Jung JY, Kang YA, Kim YS, Kim SK, Chang J, Park MS - Tuberc Respir Dis (Seoul) (2015)

The effects of ephrinA1-mediated activation of EphA2 on the phosphoinositide 3-kinase (PI3K)/Akt signaling pathways in lipopolysaccharide (LPS)-induced lung injury. EphA2-ephrinA1 signaling may contribute to the development of LPS-induced lung injury. Exposure to LPS resulted in activation of the EphA2-ephrinA1 and PI3K/Akt/nuclear factor κB (NF-κB) signaling pathway. EphA2 monoclonal antibody-induced inhibition of EphA2 signaling resulted in decreased PI3K/Akt/NF-κB-dependent inflammatory processes. These results suggested crosstalk between EphA2 signaling and PI3K/Akt/NF-κB signaling in LPS-induced lung injury. TNF-α: tumor necrosis factor α; IL: interleukin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4499589&req=5

Figure 7: The effects of ephrinA1-mediated activation of EphA2 on the phosphoinositide 3-kinase (PI3K)/Akt signaling pathways in lipopolysaccharide (LPS)-induced lung injury. EphA2-ephrinA1 signaling may contribute to the development of LPS-induced lung injury. Exposure to LPS resulted in activation of the EphA2-ephrinA1 and PI3K/Akt/nuclear factor κB (NF-κB) signaling pathway. EphA2 monoclonal antibody-induced inhibition of EphA2 signaling resulted in decreased PI3K/Akt/NF-κB-dependent inflammatory processes. These results suggested crosstalk between EphA2 signaling and PI3K/Akt/NF-κB signaling in LPS-induced lung injury. TNF-α: tumor necrosis factor α; IL: interleukin.
Mentions: EphrinA1-dependent EphA2 activation may be an unrecognized contributor to LPS-induced lung injury. Antagonizing EphA2 not only resulted in diminished expression of the PI3Kγ isoform, but it also led to decreased NF-κB activation and expression of proinflammatory cytokines through the PI3K-Akt pathway. Crosstalk of EphA2 signaling with the PI3K-Akt pathway may contribute to the neutrophil-driven inflammatory process in LPS-induced lung injury (Figure 7).

Bottom Line: 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.Furthermore, EphA2 antagonism inhibits the phosphoinositide 3-kinase-Akt pathway and attenuates inflammation.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

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: 11.33×10(4)±8.84×10(4) vs. IgG+LPS: 208.0×10(4)±122.6×10(4); 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.

No MeSH data available.


Related in: MedlinePlus