Limits...
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 cytokines (interleukin [IL]-1β, IL-6, KC, macrophage inflammatory protein 2 [MIP-2], and tumor necrosis factor α [TNF-α]) in response to EphA2 monoclonal antibody pretreatment in a lipopolysaccharide (LPS) induced lung injury model. Enzyme linked immunosorbent assay measurement showed differential expression of cytokines (IL-1β, IL-6, KC, MIP-2, and TNF-α) in lung tissue lysates. Cytokine levels were reduced in response to LPS exposure in mice with EphA2 monoclonal antibody pretreatment, as compared to those with IgG pretreatment (n=3 per group). Values are presented as mean±SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4499589&req=5

Figure 6: The expression of cytokines (interleukin [IL]-1β, IL-6, KC, macrophage inflammatory protein 2 [MIP-2], and tumor necrosis factor α [TNF-α]) in response to EphA2 monoclonal antibody pretreatment in a lipopolysaccharide (LPS) induced lung injury model. Enzyme linked immunosorbent assay measurement showed differential expression of cytokines (IL-1β, IL-6, KC, MIP-2, and TNF-α) in lung tissue lysates. Cytokine levels were reduced in response to LPS exposure in mice with EphA2 monoclonal antibody pretreatment, as compared to those with IgG pretreatment (n=3 per group). Values are presented as mean±SD.

Mentions: To determine whether EphA2 mAb has a protective function in inflammatory response, we assessed the expression of p65 NF-κB, IκB protein and cytokine levels (IL-1β, IL-6, KC, MIP-2, and TNF-α) by Western blot analysis and ELISA. EphA2 antagonism led to a decrease of p65 NF-κB and cytokine production in the EphA2 mAb+LPS group compared to the IgG+LPS group (Figures 5B, 5C, 6).


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 cytokines (interleukin [IL]-1β, IL-6, KC, macrophage inflammatory protein 2 [MIP-2], and tumor necrosis factor α [TNF-α]) in response to EphA2 monoclonal antibody pretreatment in a lipopolysaccharide (LPS) induced lung injury model. Enzyme linked immunosorbent assay measurement showed differential expression of cytokines (IL-1β, IL-6, KC, MIP-2, and TNF-α) in lung tissue lysates. Cytokine levels were reduced in response to LPS exposure in mice with EphA2 monoclonal antibody pretreatment, as compared to those with IgG pretreatment (n=3 per group). Values are presented as mean±SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: The expression of cytokines (interleukin [IL]-1β, IL-6, KC, macrophage inflammatory protein 2 [MIP-2], and tumor necrosis factor α [TNF-α]) in response to EphA2 monoclonal antibody pretreatment in a lipopolysaccharide (LPS) induced lung injury model. Enzyme linked immunosorbent assay measurement showed differential expression of cytokines (IL-1β, IL-6, KC, MIP-2, and TNF-α) in lung tissue lysates. Cytokine levels were reduced in response to LPS exposure in mice with EphA2 monoclonal antibody pretreatment, as compared to those with IgG pretreatment (n=3 per group). Values are presented as mean±SD.
Mentions: To determine whether EphA2 mAb has a protective function in inflammatory response, we assessed the expression of p65 NF-κB, IκB protein and cytokine levels (IL-1β, IL-6, KC, MIP-2, and TNF-α) by Western blot analysis and ELISA. EphA2 antagonism led to a decrease of p65 NF-κB and cytokine production in the EphA2 mAb+LPS group compared to the IgG+LPS group (Figures 5B, 5C, 6).

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