HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/5/L816    most recent 00466.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Medjane, S. Articles by Touqui, L. Search for Related Content PubMed PubMed Citation Articles by Medjane, S. Articles by Touqui, L.

Impact of CFTR F508 mutation on prostaglandin E₂ production and type IIA phospholipase A₂ expression by pulmonary epithelial cells

Institut Pasteur, Unité de Défense Innée et Inflammation; and Institut National de la Santé et de la Recherche Médicale, E336, Paris, France

Submitted 15 December 2004 ; accepted in final form 14 June 2005

Cystic fibrosis (CF) is characterized by an exacerbated inflammatory pulmonary response with excessive production of inflammatory mediators. We investigated here the impact of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction on prostaglandin E₂ (PGE₂) production and type IIA secreted phospholipase A₂ (sPLA₂-IIA) expression. We show that both resting and LPS-stimulated human respiratory epithelial cell line bearing F508 mutation on CFTR (CF cells) released more PGE₂ than control cell line. This was accompanied by enhanced expression and activity of cyclooxygenase-2 in CF cells. PGE₂ release was attenuated after experimentally induced retrafficking of the F508-CFTR at the plasma membrane. sPLA₂-IIA expression occurred at higher levels in CF cells than in control cells and was enhanced by LPS and PGE₂. Suppression of PGE₂ synthesis by aspirin led to an inhibition of LPS-induced sPLA₂-IIA expression. Higher activation of NF-B was observed in CF cells compared with control cells and was enhanced by LPS. However, addition of PGE₂ or aspirin had no effect on NF-B activation. LPS-induced sPLA₂-IIA expression was reduced by an NF-B inhibitor. We suggest that the lack of the CFTR in the plasma membrane results in a PGE₂ overproduction and an enhanced sPLA₂-IIA expression. This expression is upregulated by NF-B and amplified by PGE₂ via a unidentified signaling pathway.

cystic fibrosis; inflammation; arachidonic acid metabolism; cystic fibrosis transmembrane conductance regulator

This article has been cited by other articles:

				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]

				C. H. Serezani, M. N. Ballinger, D. M. Aronoff, and M. Peters-Golden Cyclic AMP: Master Regulator of Innate Immune Cell Function Am. J. Respir. Cell Mol. Biol., August 1, 2008; 39(2): 127 - 132. [Abstract] [Full Text] [PDF]

				B. P. Hurley and B. A. McCormick Multiple Roles of Phospholipase A2 during Lung Infection and Inflammation Infect. Immun., June 1, 2008; 76(6): 2259 - 2272. [Full Text] [PDF]

				N. Vij, M. O. Amoako, S. Mazur, and P. L. Zeitlin CHOP Transcription Factor Mediates IL-8 Signaling in Cystic Fibrosis Bronchial Epithelial Cells Am. J. Respir. Cell Mol. Biol., February 1, 2008; 38(2): 176 - 184. [Abstract] [Full Text] [PDF]