Document Detail


Ozone-induced lung injury and sterile inflammation. Role of toll-like receptor 4.
MedLine Citation:
PMID:  22300504     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Inhalation of toxic doses of ozone is associated with a sterile inflammatory response characterized by an accumulation of macrophages in the lower lung which are activated to release cytotoxic/proinflammatory mediators that contribute to tissue injury. Toll-like receptor 4 (TLR4) is a pattern recognition receptor present on macrophages that has been implicated in sterile inflammatory responses. In the present studies we used TLR4 mutant C3H/HeJ mice to analyze the role of TLR4 in ozone-induced lung injury, oxidative stress and inflammation. Acute exposure of control C3H/HeOuJ mice to ozone (0.8ppm for 3h) resulted in increases in bronchoalveolar lavage (BAL) lipocalin 24p3 and 4-hydroxynonenal modified protein, markers of oxidative stress and lipid peroxidation. This was correlated with increases in BAL protein, as well as numbers of alveolar macrophages. Levels of surfactant protein-D, a pulmonary collectin known to regulate macrophage inflammatory responses also increased in BAL following ozone inhalation. Ozone inhalation was associated with classical macrophage activation, as measured by increased NF-κB binding activity and expression of TNFα mRNA. The observation that these responses to ozone were not evident in TLR4 mutant C3H/HeJ mice demonstrates that functional TLR4 contributes to ozone-induced sterile inflammation and macrophage activation.
Authors:
Agnieszka J Connor; Jeffrey D Laskin; Debra L Laskin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-24
Journal Detail:
Title:  Experimental and molecular pathology     Volume:  -     ISSN:  1096-0945     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-2-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370711     Medline TA:  Exp Mol Pathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
Affiliation:
Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA.
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