help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on August 20, 2007, doi:10.1165/rcmb.2007-0197OC

Am. J. Respir. Cell Mol. Biol., Volume 38, Number 2, February 2008, 176-184

A more recent version of this article appeared on February 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2007-0197OCv1
38/2/176    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vij, N.
Right arrow Articles by Zeitlin, P. L
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vij, N.
Right arrow Articles by Zeitlin, P. L

Submitted on June 4, 2007
Revised on August 15, 2007

CHOP Transcription Factor Mediates IL-8 Signaling in Cystic Fibrosis Bronchial Epithelial Cells

Neeraj Vij1, Martha O Amoako1, Steven Mazur1, and Pamela L Zeitlin1*

1 Division of Pediatric Respiratory Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA

* To whom correspondence should be addressed. E-mail: pzeitlin{at}jhmi.edu.

Interleukin (IL)-8 is a potent neutrophil chemo-attractant that drives the inflammatory response in cystic fibrosis. Traditional approaches to the pathophysiology of this inflammation have focused on targeting NF{kappa}B-dependent signaling and therapy with glucocorticoids. We test the hypothesis that an alternative pathway, independent of NF{kappa}B, 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 cyclo-oxygenase (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 CHOP (C/EBP homologous protein) 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.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
M. Cucinotta, M. Visalli, M. Aguennouz, A. Valenti, S. Loddo, L. Altucci, and D. Teti
Regulation of Interleukin-8 Gene at a Distinct Site of Its Promoter by CCAAT Enhancer-binding Protein Homologous Protein in Prostaglandin E2-treated Human T Cells
J. Biol. Chem., October 31, 2008; 283(44): 29760 - 29769.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
T. Roque, E. Boncoeur, V. Saint-Criq, E. Bonvin, A. Clement, O. Tabary, and J. Jacquot
Proinflammatory Effect of Sodium 4-Phenylbutyrate in {Delta}F508-Cystic Fibrosis Transmembrane Conductance Regulator Lung Epithelial Cells: Involvement of Extracellular Signal-Regulated Protein Kinase 1/2 and c-Jun-NH2-Terminal Kinase Signaling
J. Pharmacol. Exp. Ther., September 1, 2008; 326(3): 949 - 956.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. J. Blohmke, R. E. Victor, A. F. Hirschfeld, I. M. Elias, D. G. Hancock, C. R. Lane, A. G. F. Davidson, P. G. Wilcox, K. D. Smith, J. Overhage, et al.
Innate Immunity Mediated by TLR5 as a Novel Antiinflammatory Target for Cystic Fibrosis Lung Disease
J. Immunol., June 1, 2008; 180(11): 7764 - 7773.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2007 American Thoracic Society. 		  CCM abstracts