| Carbonylation caused by cigarette smoke extract is associated with defective macrophage immunity. | |
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MedLine Citation:
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PMID: 20935190 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Oxidants in cigarette smoke inhibit pathogen recognition receptor function and phagocytosis, but the molecular basis of this inhibition remains obscure. We sought to identify the inhibitory mechanisms that impair alveolar macrophage function. Balb/c mice were acutely exposed to four cigarettes for 4 hours before treatment with intranasal LPS (1 μg). The mice exhibited significantly reduced airway neutrophilia and expression of TNF-α. Balb/c-derived MH-S alveolar macrophage cells exposed to cigarette smoke extract (CSE) displayed a similar inhibitory response to stimulation with LPS. The induction of inflammatory genes by recombinant (r) TNF-α (100 ng/ml) was also impaired by CSE. Because both pathways converge on NF-κB, the degradation of IκBα and the phosphorylation of p65 were assessed and shown to be blunted by CSE. CSE also blocked the activity of activator protein-1 (AP-1) by inhibiting p38 mitogen activated protein kinase (MAPK) in a reduced glutathione (GSH)-reversible manner. The induction of specific Toll-like receptor (TLR)-negative regulators (suppressor of cytokine signaling-1 [SOCS-1], interleukin-1 receptor associated kinase-M [IRAK-M], and IL-10) did not account for the impaired responses of TLRs. As free radical species are abundant in CSE and GSH restored function, a panel of oxidative/nitrosative stress markers was screened using immunocytochemistry. The panel identified protein carbonylation as the major CSE-inducible marker. Oxyblot analysis confirmed that CSE potently introduced carbonyl groups to many proteins in a dose-dependent and time-dependent manner that inversely correlated with the expression of TNF-α. The formation of pseudopodia was not prevented, but these membrane extensions were heavily carbonylated, and primary alveolar macrophages were also targeted for carbonylation. Oxidants in cigarette smoke drive a rapid, persistent, and global protein carbonylation that may represent a common pathway to altered immunity in disease. |
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Authors:
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Steven Bozinovski; Ross Vlahos; Yilin Zhang; Lin Chin Lah; Huei Jiunn Seow; Ashley Mansell; Gary P Anderson |
Publication Detail:
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Type: Journal Article Date: 2010-10-08 |
Journal Detail:
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Title: American journal of respiratory cell and molecular biology Volume: 45 ISSN: 1535-4989 ISO Abbreviation: Am. J. Respir. Cell Mol. Biol. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-08-04 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8917225 Medline TA: Am J Respir Cell Mol Biol Country: United States |
Other Details:
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Languages: eng Pagination: 229-36 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, University of Melbourne, Melbourne 3010, Victoria, Australia. bozis@unimelb.edu.au. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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