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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 expression of EphA2 and ephrinA1 in lung lysates after lipopolysaccharide (LPS) exposure, as shown by Western blots (A) and densitometry (B, C). IgG pretreatment increased the expression of EphA2 and ephrinA1 after LPS exposure; whereas, EphA2 monoclonal antibody pretreatment reduced the expression of EphA2 and ephrinA1 after LPS exposure. Values are presented as mean±SD. PBS: phosphate buffered saline.
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Figure 1: The expression of EphA2 and ephrinA1 in lung lysates after lipopolysaccharide (LPS) exposure, as shown by Western blots (A) and densitometry (B, C). IgG pretreatment increased the expression of EphA2 and ephrinA1 after LPS exposure; whereas, EphA2 monoclonal antibody pretreatment reduced the expression of EphA2 and ephrinA1 after LPS exposure. Values are presented as mean±SD. PBS: phosphate buffered saline.

Mentions: As shown in Figure 1, Western blotting studies demonstrated a significant increase in EphA2 and ephrinA1 protein expression after LPS challenge. Both EphA2 and ephrinA1 protein expression were reduced when EphA2 mAb was instilled as pretreatment. Also, the degree of decline was higher in the 4 µg EphA2 mAb subgroup than the 2 µg mAb subgroup in both EphA2 and ephrinA1 (Figure 1).


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 expression of EphA2 and ephrinA1 in lung lysates after lipopolysaccharide (LPS) exposure, as shown by Western blots (A) and densitometry (B, C). IgG pretreatment increased the expression of EphA2 and ephrinA1 after LPS exposure; whereas, EphA2 monoclonal antibody pretreatment reduced the expression of EphA2 and ephrinA1 after LPS exposure. Values are presented as mean±SD. PBS: phosphate buffered saline.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: The expression of EphA2 and ephrinA1 in lung lysates after lipopolysaccharide (LPS) exposure, as shown by Western blots (A) and densitometry (B, C). IgG pretreatment increased the expression of EphA2 and ephrinA1 after LPS exposure; whereas, EphA2 monoclonal antibody pretreatment reduced the expression of EphA2 and ephrinA1 after LPS exposure. Values are presented as mean±SD. PBS: phosphate buffered saline.
Mentions: As shown in Figure 1, Western blotting studies demonstrated a significant increase in EphA2 and ephrinA1 protein expression after LPS challenge. Both EphA2 and ephrinA1 protein expression were reduced when EphA2 mAb was instilled as pretreatment. Also, the degree of decline was higher in the 4 µg EphA2 mAb subgroup than the 2 µg mAb subgroup in both EphA2 and ephrinA1 (Figure 1).

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