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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 effect of EphA2 monoclonal antibody pretreatment on semiquantitative lung injury scores (A), total bronchoalveolar fluid (BALF) cell count (B) and BALF protein concentration (C). In the lipopolysaccharide (LPS)-induced lung injury model, EphA2 antagonism with EphA2 monoclonal antibody led to improved lung injury scores, decreased BALF cell counts and decreased BALF proteins (p<0.05, except BALF protein), as compared to IgG pretreatment. Values are presented as mean±SD (n=4 per group).
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Figure 3: The effect of EphA2 monoclonal antibody pretreatment on semiquantitative lung injury scores (A), total bronchoalveolar fluid (BALF) cell count (B) and BALF protein concentration (C). In the lipopolysaccharide (LPS)-induced lung injury model, EphA2 antagonism with EphA2 monoclonal antibody led to improved lung injury scores, decreased BALF cell counts and decreased BALF proteins (p<0.05, except BALF protein), as compared to IgG pretreatment. Values are presented as mean±SD (n=4 per group).

Mentions: Figure 3 shows the lung injury scores, bronchoalveolar lavage cell counts and protein concentrations of the four groups. The lung injury score of the EphA2 mAb 4 µg+LPS group was lower than that of the IgG+LPS group (4.30±2.93 vs.11.45±1.20, respectively; p=0.004). LPS caused a significant increase in cell counts and concentration of total protein in the lung lavage fluid. LPS-induced lung injury was attenuated by pretreatment with EphA2 mAb. Cell counts were significantly less (EphA2 mAb 4 µg+LPS: 11.33×104±8.84×104 vs. IgG+LPS: 208.0×104±122.6×104; p=0.018) and concentrations of total protein were lower (EphA2 mAb 4 µg+LPS: 0.52±0.41 mg/mL vs. IgG+LPS: 1.38±1.08 mg/mL; p=0.192) in EphA2 mAb+LPS group, compared with IgG+LPS group.


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 effect of EphA2 monoclonal antibody pretreatment on semiquantitative lung injury scores (A), total bronchoalveolar fluid (BALF) cell count (B) and BALF protein concentration (C). In the lipopolysaccharide (LPS)-induced lung injury model, EphA2 antagonism with EphA2 monoclonal antibody led to improved lung injury scores, decreased BALF cell counts and decreased BALF proteins (p<0.05, except BALF protein), as compared to IgG pretreatment. Values are presented as mean±SD (n=4 per group).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: The effect of EphA2 monoclonal antibody pretreatment on semiquantitative lung injury scores (A), total bronchoalveolar fluid (BALF) cell count (B) and BALF protein concentration (C). In the lipopolysaccharide (LPS)-induced lung injury model, EphA2 antagonism with EphA2 monoclonal antibody led to improved lung injury scores, decreased BALF cell counts and decreased BALF proteins (p<0.05, except BALF protein), as compared to IgG pretreatment. Values are presented as mean±SD (n=4 per group).
Mentions: Figure 3 shows the lung injury scores, bronchoalveolar lavage cell counts and protein concentrations of the four groups. The lung injury score of the EphA2 mAb 4 µg+LPS group was lower than that of the IgG+LPS group (4.30±2.93 vs.11.45±1.20, respectively; p=0.004). LPS caused a significant increase in cell counts and concentration of total protein in the lung lavage fluid. LPS-induced lung injury was attenuated by pretreatment with EphA2 mAb. Cell counts were significantly less (EphA2 mAb 4 µg+LPS: 11.33×104±8.84×104 vs. IgG+LPS: 208.0×104±122.6×104; p=0.018) and concentrations of total protein were lower (EphA2 mAb 4 µg+LPS: 0.52±0.41 mg/mL vs. IgG+LPS: 1.38±1.08 mg/mL; p=0.192) in EphA2 mAb+LPS group, compared with IgG+LPS group.

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