Pseudomonas aeruginosa-induced apoptosis in airway epithelial cells is mediated by gap junctional communication in a JNK-dependent manner

Losa, D; Köhler, T; Bellec, J; Dudez, T; Crespin, S; Bacchetta, M; Boulanger, P; Hong, SS; Morel, S; Nguyen, TH; Van Delden, C; Chanson, M

Pseudomonas aeruginosa-induced apoptosis in airway epithelial cells is mediated by gap junctional communication in a JNK-dependent manner

Losa, D

Köhler, T Bellec, J Dudez, T Crespin, S Bacchetta, M Boulanger, P Hong, SS Morel, S Nguyen, TH Van Delden, C Chanson, M

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Publication Type:: Journal Article
Citation:: Journal of Immunology, 2014, 192 (10), pp. 4804 - 4812
Issue Date:: 2014-05-15

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Field	Value	Language
dc.contributor.author	Losa, D https://orcid.org/0000-0001-5219-3244	en_US
dc.contributor.author	Köhler, T	en_US
dc.contributor.author	Bellec, J	en_US
dc.contributor.author	Dudez, T	en_US
dc.contributor.author	Crespin, S	en_US
dc.contributor.author	Bacchetta, M	en_US
dc.contributor.author	Boulanger, P	en_US
dc.contributor.author	Hong, SS	en_US
dc.contributor.author	Morel, S	en_US
dc.contributor.author	Nguyen, TH	en_US
dc.contributor.author	Van Delden, C	en_US
dc.contributor.author	Chanson, M	en_US
dc.date.issued	2014-05-15	en_US
dc.identifier.citation	Journal of Immunology, 2014, 192 (10), pp. 4804 - 4812	en_US
dc.identifier.issn	0022-1767	en_US
dc.identifier.uri	http://hdl.handle.net/10453/117843
dc.description.abstract	Chronic infection and inflammation of the airways is a hallmark of cystic fibrosis (CF), a disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. The response of the CF airway epithelium to the opportunistic pathogen Pseudomonas aeruginosa is characterized by altered inflammation and apoptosis. In this study, we examined innate immune recognition and epithelial responses at the level of the gap junction protein connexin43 (Cx43) in polarized human airway epithelial cells upon infection by PAO1. We report that PAO1 activates cell surface receptors to elicit an intracellular signaling cascade leading to enhancement of gap junctional communication. Expression of Cx43 involved an opposite regulation exerted by JNK and p38 MAPKs. PAO1-induced apoptosis was increased in the presence of a JNK inhibitor, but latter effect was prevented by lentiviral expression of a Cx43-specific short hairpin RNA. Moreover, we found that JNK activity was upregulated by pharmacological inhibition of CFTR in Calu-3 cells, whereas correction of a CF airway cell line (CF15 cells) by adenoviral expression of CFTR reduced the activation of this MAPK. Interestingly, CFTR inhibition in Calu-3 cells was associated with decreased Cx43 expression and reduced apoptosis. These results indicate that Cx43 expression is a component of the response of airway epithelial cells to innate immune activation by regulating the survival/apoptosis balance. Defective CFTR could alter this equilibrium with deleterious consequences on the CF epithelial response to P. aeruginosa. Copyright © 2014 by The American Association of Immunologists, Inc.	en_US
dc.relation.ispartof	Journal of Immunology	en_US
dc.relation.isbasedon	10.4049/jimmunol.1301294	en_US
dc.subject.classification	Immunology	en_US
dc.subject.mesh	Respiratory Mucosa	en_US
dc.subject.mesh	Cell Line	en_US
dc.subject.mesh	Gap Junctions	en_US
dc.subject.mesh	Epithelial Cells	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Pseudomonas aeruginosa	en_US
dc.subject.mesh	Pseudomonas Infections	en_US
dc.subject.mesh	Cystic Fibrosis	en_US
dc.subject.mesh	MAP Kinase Kinase 4	en_US
dc.subject.mesh	p38 Mitogen-Activated Protein Kinases	en_US
dc.subject.mesh	Cystic Fibrosis Transmembrane Conductance Regulator	en_US
dc.subject.mesh	Connexin 43	en_US
dc.subject.mesh	Cell Communication	en_US
dc.subject.mesh	Apoptosis	en_US
dc.subject.mesh	MAP Kinase Signaling System	en_US
dc.title	Pseudomonas aeruginosa-induced apoptosis in airway epithelial cells is mediated by gap junctional communication in a JNK-dependent manner	en_US
dc.type	Journal Article
utslib.citation.volume	10	en_US
utslib.citation.volume	192	en_US
utslib.for	1107 Immunology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	closed_access
pubs.issue	10	en_US
pubs.publication-status	Published	en_US
pubs.volume	192	en_US

Abstract:

Chronic infection and inflammation of the airways is a hallmark of cystic fibrosis (CF), a disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. The response of the CF airway epithelium to the opportunistic pathogen Pseudomonas aeruginosa is characterized by altered inflammation and apoptosis. In this study, we examined innate immune recognition and epithelial responses at the level of the gap junction protein connexin43 (Cx43) in polarized human airway epithelial cells upon infection by PAO1. We report that PAO1 activates cell surface receptors to elicit an intracellular signaling cascade leading to enhancement of gap junctional communication. Expression of Cx43 involved an opposite regulation exerted by JNK and p38 MAPKs. PAO1-induced apoptosis was increased in the presence of a JNK inhibitor, but latter effect was prevented by lentiviral expression of a Cx43-specific short hairpin RNA. Moreover, we found that JNK activity was upregulated by pharmacological inhibition of CFTR in Calu-3 cells, whereas correction of a CF airway cell line (CF15 cells) by adenoviral expression of CFTR reduced the activation of this MAPK. Interestingly, CFTR inhibition in Calu-3 cells was associated with decreased Cx43 expression and reduced apoptosis. These results indicate that Cx43 expression is a component of the response of airway epithelial cells to innate immune activation by regulating the survival/apoptosis balance. Defective CFTR could alter this equilibrium with deleterious consequences on the CF epithelial response to P. aeruginosa. Copyright © 2014 by The American Association of Immunologists, Inc.

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http://hdl.handle.net/10453/117843