Lipoxin A4 stimulates calcium-activated chloride currents and increases airway surface liquid height in normal and cystic fibrosis airway epithelia.

Hdl Handle:
http://hdl.handle.net/10147/264501
Title:
Lipoxin A4 stimulates calcium-activated chloride currents and increases airway surface liquid height in normal and cystic fibrosis airway epithelia.
Authors:
Verrière, Valia; Higgins, Gerard; Al-Alawi, Mazen; Costello, Richard W; McNally, Paul; Chiron, Raphaël; Harvey, Brian J; Urbach, Valérie
Affiliation:
Department of Molecular Medicine, RCSI Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
Citation:
Lipoxin A4 stimulates calcium-activated chloride currents and increases airway surface liquid height in normal and cystic fibrosis airway epithelia. 2012, 7 (5):e37746 PLoS ONE
Journal:
PloS one
Issue Date:
2012
URI:
http://hdl.handle.net/10147/264501
DOI:
10.1371/journal.pone.0037746
PubMed ID:
22662206
Abstract:
Cystic Fibrosis (CF) is a genetic disease characterised by a deficit in epithelial Cl(-) secretion which in the lung leads to airway dehydration and a reduced Airway Surface Liquid (ASL) height. The endogenous lipoxin LXA(4) is a member of the newly identified eicosanoids playing a key role in ending the inflammatory process. Levels of LXA(4) are reported to be decreased in the airways of patients with CF. We have previously shown that in normal human bronchial epithelial cells, LXA(4) produced a rapid and transient increase in intracellular Ca(2+). We have investigated, the effect of LXA(4) on Cl(-) secretion and the functional consequences on ASL generation in bronchial epithelial cells obtained from CF and non-CF patient biopsies and in bronchial epithelial cell lines. We found that LXA(4) stimulated a rapid intracellular Ca(2+) increase in all of the different CF bronchial epithelial cells tested. In non-CF and CF bronchial epithelia, LXA(4) stimulated whole-cell Cl(-) currents which were inhibited by NPPB (calcium-activated Cl(-) channel inhibitor), BAPTA-AM (chelator of intracellular Ca(2+)) but not by CFTRinh-172 (CFTR inhibitor). We found, using confocal imaging, that LXA(4) increased the ASL height in non-CF and in CF airway bronchial epithelia. The LXA(4) effect on ASL height was sensitive to bumetanide, an inhibitor of transepithelial Cl(-) secretion. The LXA(4) stimulation of intracellular Ca(2+), whole-cell Cl(-) currents, conductances and ASL height were inhibited by Boc-2, a specific antagonist of the ALX/FPR2 receptor. Our results provide, for the first time, evidence for a novel role of LXA(4) in the stimulation of intracellular Ca(2+) signalling leading to Ca(2+)-activated Cl(-) secretion and enhanced ASL height in non-CF and CF bronchial epithelia.
Item Type:
Article
Language:
en
MeSH:
Anti-Inflammatory Agents, Non-Steroidal; Calcium; Child, Preschool; Chlorides; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Dose-Response Relationship, Drug; Epithelial Cells; Humans; Lipoxins; Primary Cell Culture; Receptors, Formyl Peptide; Receptors, Lipoxin; Respiratory Mucosa
ISSN:
1932-6203

Full metadata record

DC FieldValue Language
dc.contributor.authorVerrière, Valiaen_GB
dc.contributor.authorHiggins, Gerarden_GB
dc.contributor.authorAl-Alawi, Mazenen_GB
dc.contributor.authorCostello, Richard Wen_GB
dc.contributor.authorMcNally, Paulen_GB
dc.contributor.authorChiron, Raphaëlen_GB
dc.contributor.authorHarvey, Brian Jen_GB
dc.contributor.authorUrbach, Valérieen_GB
dc.date.accessioned2013-01-08T15:49:52Z-
dc.date.available2013-01-08T15:49:52Z-
dc.date.issued2012-
dc.identifier.citationLipoxin A4 stimulates calcium-activated chloride currents and increases airway surface liquid height in normal and cystic fibrosis airway epithelia. 2012, 7 (5):e37746 PLoS ONEen_GB
dc.identifier.issn1932-6203-
dc.identifier.pmid22662206-
dc.identifier.doi10.1371/journal.pone.0037746-
dc.identifier.urihttp://hdl.handle.net/10147/264501-
dc.description.abstractCystic Fibrosis (CF) is a genetic disease characterised by a deficit in epithelial Cl(-) secretion which in the lung leads to airway dehydration and a reduced Airway Surface Liquid (ASL) height. The endogenous lipoxin LXA(4) is a member of the newly identified eicosanoids playing a key role in ending the inflammatory process. Levels of LXA(4) are reported to be decreased in the airways of patients with CF. We have previously shown that in normal human bronchial epithelial cells, LXA(4) produced a rapid and transient increase in intracellular Ca(2+). We have investigated, the effect of LXA(4) on Cl(-) secretion and the functional consequences on ASL generation in bronchial epithelial cells obtained from CF and non-CF patient biopsies and in bronchial epithelial cell lines. We found that LXA(4) stimulated a rapid intracellular Ca(2+) increase in all of the different CF bronchial epithelial cells tested. In non-CF and CF bronchial epithelia, LXA(4) stimulated whole-cell Cl(-) currents which were inhibited by NPPB (calcium-activated Cl(-) channel inhibitor), BAPTA-AM (chelator of intracellular Ca(2+)) but not by CFTRinh-172 (CFTR inhibitor). We found, using confocal imaging, that LXA(4) increased the ASL height in non-CF and in CF airway bronchial epithelia. The LXA(4) effect on ASL height was sensitive to bumetanide, an inhibitor of transepithelial Cl(-) secretion. The LXA(4) stimulation of intracellular Ca(2+), whole-cell Cl(-) currents, conductances and ASL height were inhibited by Boc-2, a specific antagonist of the ALX/FPR2 receptor. Our results provide, for the first time, evidence for a novel role of LXA(4) in the stimulation of intracellular Ca(2+) signalling leading to Ca(2+)-activated Cl(-) secretion and enhanced ASL height in non-CF and CF bronchial epithelia.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to PloS oneen_GB
dc.subject.meshAnti-Inflammatory Agents, Non-Steroidal-
dc.subject.meshCalcium-
dc.subject.meshChild, Preschool-
dc.subject.meshChlorides-
dc.subject.meshCystic Fibrosis-
dc.subject.meshCystic Fibrosis Transmembrane Conductance Regulator-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshEpithelial Cells-
dc.subject.meshHumans-
dc.subject.meshLipoxins-
dc.subject.meshPrimary Cell Culture-
dc.subject.meshReceptors, Formyl Peptide-
dc.subject.meshReceptors, Lipoxin-
dc.subject.meshRespiratory Mucosa-
dc.titleLipoxin A4 stimulates calcium-activated chloride currents and increases airway surface liquid height in normal and cystic fibrosis airway epithelia.en_GB
dc.typeArticleen
dc.contributor.departmentDepartment of Molecular Medicine, RCSI Education and Research Centre, Beaumont Hospital, Dublin, Ireland.en_GB
dc.identifier.journalPloS oneen_GB
dc.description.provinceLeinsteren

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