Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10757001 | Biochemical and Biophysical Research Communications | 2013 | 4 Pages |
Abstract
Excessive inflammation and Pseudomonas aeruginosa infection are two major characteristics of cystic fibrosis (CF) lung disease. In this manuscript, we describe a novel mechanism of ERK1/ERK2 activation and CXCL8 expression in airway epithelial cells (AECs) lacking functional CFTR. In both non-CF and CF AECs, 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.
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Authors
Guy Martel, Lucie Roussel, Simon Rousseau,