CHOP transcription factor mediates IL-8 signaling in cystic fibrosis bronchial epithelial cells.
Am J Respir Cell Mol Biol
; 38(2): 176-84, 2008 Feb.
Article
em En
| MEDLINE
| ID: mdl-17709599
ABSTRACT
Interleukin (IL)-8 is a potent neutrophil chemoattractant that drives the inflammatory response in cystic fibrosis (CF). Traditional approaches to the pathophysiology of this inflammation have focused on targeting NF-kappaB-dependent signaling and therapy with glucocorticoids. We test the hypothesis that an alternative pathway, independent of NF-kappaB, operates through prostaglandin E2 (PGE-2) receptor EP-2 and stimulates IL-8 chemokine secretion. Using CF bronchial epithelial cells (IB3-1) in vitro, exogenous PGE-2 induces IL-8 release in a dose-dependent manner. These events are associated with elevation in the EP-2 receptors. Inhibition of cyclooxygenase (Cox)-2 with NS-398 was associated with reductions in Cox-2 (2-fold) and IL-6 (1.3-fold) mRNA transcripts, and in IL-8 and PGE-2 chemokine secretion. The inhibition of Cox-2 signaling led to down-regulation of the downstream C/EBP homologous protein (CHOP) transcription factor, resulting in a decrease in IL-8 activation. We confirmed the regulation of IL-8 promoter by CHOP in CF cells using the IL-8 reporter assay. We conclude that PGE-2 stimulates IL-8 production through the CHOP transcription factor in CF cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Brônquios
/
Transdução de Sinais
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Interleucina-8
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Fibrose Cística
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Fator de Transcrição CHOP
Limite:
Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article