The protein kinases TPL2 and EGFR contribute to ERK1/ERK2 hyperactivation in CFTRΔF508-expressing airway epithelial cells exposed to Pseudomonas aeruginosa.
Biochem Biophys Res Commun
; 441(3): 689-92, 2013 Nov 22.
Article
em En
| MEDLINE
| ID: mdl-24404585
ABSTRACT
Excessive inflammation and Pseudomonas aeruginosa infection are two major characteristics of cysticfibrosis (CF) lung disease. In this manuscript, we describe a novel mechanism of ERK1/ERK2 activationand CXCL8 expression in airway epithelial cells (AECs) lacking functional CFTR. In both non-CF and CFAECs, the protein kinase TPL2 is required for ERK1/ERK2 MAPK activation. However, we have found that EGFR is strongly phosphorylated in the airway epithelium of CF lung and contributes to ERK1/ERK2 MAPK activation in CF AECs exposed to P. aeruginosa diffusible material (PsaDM). Moreover, PsaDM stimulates the expression of the EGFR pro-ligand HB-EGF more strongly, and in a sustained manner, in CF AECs compared to non-CF cells. Finally, although both non-CF and CF AECs expresses CXCL8 in response to PsaDM, the levels of CXCL8 are higher and EGFR plays a more important role in regulating CXCL8 synthesis in CF AECs. Together, our finding shows that in addition to the TLR-mediated TPL2 activation of ERK1/ERK2, an additional pathway contributing to ERK1/ERK2 activation is triggered by infection of CF AECs the EGFR signaling pathway. This second pathway may contribute to excessive inflammation observed in CF.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
/
Infecções por Pseudomonas
/
Proteínas Proto-Oncogênicas
/
Regulador de Condutância Transmembrana em Fibrose Cística
/
Mucosa Respiratória
/
MAP Quinase Quinase Quinases
/
Fibrose Cística
/
Receptores ErbB
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article