| Targeted deletion of Jun/AP-1 in alveolar epithelial cells causes progressive emphysema and worsens cigarette smoke-induced lung inflammation. | |
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MedLine Citation:
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PMID: 22265050 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chronic obstructive pulmonary disease appears to occur slowly and progressively over many years, with both genetic factors and environmental modifiers contributing to its pathogenesis. Although the c-Jun/activator protein 1 transcriptional factor regulates cell proliferation, apoptosis, and inflammatory responses, its role in lung pathogenesis is largely unknown. In this study, we report decreased expression levels of c-Jun mRNA and protein in the lung tissues of patients with advanced chronic obstructive pulmonary disease, and the genetic deletion of c-Jun specifically in alveolar epithelial cells causes progressive emphysema with lung inflammation and alveolar air space enlargement, which are cardinal features of emphysema. Although mice lacking c-Jun specifically in lung alveolar epithelial cells appear normal at the age of 6 weeks, when exposed to long-term cigarette smoke, c-Jun-mutant mice display more lung inflammation with perivascular and peribronchiolar infiltrates compared with controls. These results demonstrate that the c-Jun/activator protein 1 pathway is critical for maintaining lung alveolar cell homeostasis and that loss of its expression can contribute to lung inflammation and progressive emphysema. |
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Authors:
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Narsa M Reddy; Suryanaraya Vegiraju; Ashley Irving; Bogdan C Paun; Irina G Luzina; Sergei P Atamas; Shyam Biswal; Navas-Acien Ana; Wayne Mitzner; Sekhar P Reddy |
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: 180 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-01-23 Completed Date: 2012-03-25 Revised Date: 2013-04-08 |
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: 562-74 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aged Animals Antioxidants / metabolism Cytokines / metabolism Female Gene Deletion* Gene Expression / physiology Humans Male Mice Mice, Inbred C57BL Middle Aged Pneumonia / genetics Proto-Oncogene Proteins c-jun / deficiency, genetics*, metabolism Pulmonary Alveoli / metabolism Pulmonary Disease, Chronic Obstructive / genetics*, metabolism Pulmonary Emphysema / genetics*, metabolism RNA, Messenger / metabolism Respiratory Mucosa / metabolism Smoke / adverse effects* Smoking / adverse effects, genetics Transcription Factor AP-1 / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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ES007141/ES/NIEHS NIH HHS; P50-HL073994/HL/NHLBI NIH HHS; P50HL084945/HL/NHLBI NIH HHS; R01-ES11863/ES/NIEHS NIH HHS; R01-HL66109/HL/NHLBI NIH HHS; R03-HL96933/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Cytokines; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Messenger; 0/Smoke; 0/Transcription Factor AP-1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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