| Alveolar cell senescence exacerbates pulmonary inflammation in patients with chronic obstructive pulmonary disease. | |
MedLine Citation:
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PMID: 20016134 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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BACKGROUND: Alveolar cell senescence is accelerated in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: We tested the hypothesis that alveolar cell senescence contributes to the chronic inflammation that affects the lungs of COPD patients. METHODS: We exposed alveolar type II-like epithelial (A549) cells to a G-quadruplex-interacting telomerase inhibitor in vitro to induce cellular senescence and analyzed the production of proinflammatory cytokines and the activation of NF-kappaB. Human dermal microvascular endothelial cells (HDMECs) were serially passaged to induce replicative senescence. We also immunostained human lung tissue sections obtained from COPD patients, asymptomatic smokers and asymptomatic nonsmokers and examined correlations between type II cell senescence and inflammation. RESULTS: Senescent A549 cells and HDMECs, whether stimulated with lipopolysaccharide or not, produced greater amounts of IL-6, IL-8 and TNF-alpha, which paralleled NF-kappaB activation, than did presenescent cells. There were positive correlations between the percentages of senescent type II cells that expressed p16(INK4a) and the percentages of type II cells that expressed phosphorylated NF-kappaB. The lung tissue of the COPD patients contained higher percentages of proinflammatory senescent type II cells that co-expressed p16(INK4a) and phosphorylated NF-kappaB than the tissue from asymptomatic smokers and asymptomatic nonsmokers. Higher percentages of p16(INK4a)-positive senescent type II cells than of p16(INK4a)-negative presenescent type II cells were positive for phosphorylated NF-kappaB. CONCLUSIONS: Senescence of alveolar epithelial cells is associated with functional alterations of the cells to a proinflammatory phenotype and may contribute to the pathogenesis of COPD. |
Authors:
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Takao Tsuji; Kazutetsu Aoshiba; Atsushi Nagai |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-17 |
Journal Detail:
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Title: Respiration; international review of thoracic diseases Volume: 80 ISSN: 1423-0356 ISO Abbreviation: Respiration Publication Date: 2010 |
Date Detail:
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Created Date: 2010-06-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0137356 Medline TA: Respiration Country: Switzerland |
Other Details:
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Languages: eng Pagination: 59-70 Citation Subset: IM |
Affiliation:
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First Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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