EphA2 Receptor Signaling Mediates Inflammatory Responses in Lipopolysaccharide-Induced Lung Injury / 결핵및호흡기질환
Tuberculosis and Respiratory Diseases
;
: 218-226, 2015.
Artigo
em Inglês
| WPRIM
| ID: wpr-114246
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 11.33x10(4)+/-8.84x10(4) vs. IgG+LPS 208.0x10(4)+/-122.6x10(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 110gamma, phospho-Akt, nuclear factor kappaB, 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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Axônios
/
Permeabilidade Capilar
/
Contagem de Células
/
Movimento Celular
/
Lipopolissacarídeos
/
Citocinas
/
Receptores da Família Eph
/
Receptor EphA1
/
Receptor EphA2
/
Lesão Pulmonar
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
Idioma:
Inglês
Revista:
Tuberculosis and Respiratory Diseases
Ano de publicação:
2015
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS