| Lipoxin A(4) regulates bronchial epithelial cell responses to acid injury. | |
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MedLine Citation:
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PMID: 16565483 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Aspiration of gastric acid commonly injures airway epithelium and, if severe, can lead to respiratory failure from acute respiratory distress syndrome. Recently, we identified cyclooxygenase-2 (COX-2)-derived prostaglandin E(2) (PGE(2)) and lipoxin A(4) (LXA(4)) as pivotal mediators in vivo for resolution of acid-initiated acute lung injury. To examine protective mechanisms for these mediators in the airway, we developed an in vitro model of acid injury by transiently exposing well-differentiated normal human bronchial epithelial cells to hydrochloric acid. Transmission electron microscopy revealed selective injury to superficial epithelial cells with disruption of cell attachments and cell shedding. The morphological features of injury were substantially resolved within 6 hours. Acid triggered and early marked increases in COX-2 expression and PGE(2) production, and acid-induced PGE(2) significantly increased epithelial LXA(4) receptor (ALX) expression. LXA(4) is generated in vivo during acute lung injury, and we observed that nanomolar quantities increased basal epithelial cell proliferation and potently blocked acid-triggered interleukin-6 release and neutrophil transmigration across well-differentiated normal human bronchial epithelial cells. Expression of recombinant human ALX in A549 airway epithelial cells uncovered ALX-dependent inhibition of cytokine release by LXA(4). Together, these findings indicate that injured bronchial epithelial cells up-regulate ALX in a COX-2-dependent manner to promote LXA(4)-mediated resolution of airway inflammation. |
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Authors:
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Caroline Bonnans; Koichi Fukunaga; Marilyn A Levy; Bruce D Levy |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The American journal of pathology Volume: 168 ISSN: 0002-9440 ISO Abbreviation: Am. J. Pathol. Publication Date: 2006 Apr |
Date Detail:
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Created Date: 2006-03-27 Completed Date: 2006-05-25 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 1064-72 Citation Subset: AIM; IM |
Affiliation:
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Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Bronchi
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metabolism*,
ultrastructure Cell Adhesion Cell Proliferation Cells, Cultured Cyclooxygenase 2 / biosynthesis Dinoprostone / biosynthesis Epithelial Cells / drug effects, physiology*, ultrastructure Gastric Acid / physiology* Humans Hydrochloric Acid / toxicity Lipoxins / physiology* Membrane Proteins / antagonists & inhibitors, biosynthesis Microscopy, Electron, Transmission Nitrobenzenes / pharmacology Receptors, Formyl Peptide / biosynthesis Receptors, Lipoxin / biosynthesis Respiratory Mucosa / metabolism*, ultrastructure Sulfonamides / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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AI0608084/AI/NIAID NIH HHS; DE016191/DE/NIDCR NIH HHS; HL68669/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/FPR2 protein, human; 0/Lipoxins; 0/Membrane Proteins; 0/Nitrobenzenes; 0/Receptors, Formyl Peptide; 0/Receptors, Lipoxin; 0/Sulfonamides; 0/lipoxin A4; 123653-11-2/N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; 363-24-6/Dinoprostone; 7647-01-0/Hydrochloric Acid; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human |
| Comments/Corrections | |
Comment In:
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Am J Pathol. 2006 Apr;168(4):1060-3
[PMID:
16565482
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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