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Toll-like receptor 2 regulates organic dust-induced airway inflammation.

Abstract
Organic dust exposure in agricultural environments results in significant airway inflammatory diseases. Gram-positive cell wall components are present in high concentrations in animal farming dusts, but their role in mediating dust-induced airway inflammation is not clear. This study investigated the role of Toll-like receptor (TLR) 2, a pattern recognition receptor for gram-positive cell wall products, in regulating swine facility organic dust extract (DE)-induced airway inflammation in mice. Isolated lung macrophages from TLR2 knockout mice demonstrated reduced TNF-α, IL-6, keratinocyte chemoattractant/CXCL1, but not macrophage inflammatory protein-2/CXCL2 expression, after DE stimulation ex vivo. Next, using an established mouse model of intranasal inhalation challenge, we analyzed bronchoalveolar lavage fluid and lung tissue in TLR2-deficient and wild-type (WT) mice after single and repetitive DE challenge. Neutrophil influx and select cytokines/chemokines were significantly lower in TLR2-deficient mice at 5 and 24 hours after single DE challenge. After daily exposure to DE for 2 weeks, there were significant reductions in total cellularity, neutrophil influx, and TNF-α, IL-6, CXCL1, but not CXCL2 expression, in TLR2-deficient mice as compared with WT animals. Lung pathology revealed that bronchiolar inflammation, but not alveolar inflammation, was reduced in TLR2-deficient mice after repetitive exposure. Airway hyperresponsiveness to methacholine after dust exposure was similar in both groups. Finally, airway inflammatory responses in WT mice after challenge with a TLR2 agonist, peptidoglycan, resembled DE-induced responses. Collectively, these results demonstrate that the TLR2 pathway is important in regulating swine facility organic dust-induced airway inflammation, which suggests the importance of TLR2 agonists in mediating large animal farming-induced airway inflammatory responses.
AuthorsJill A Poole, Todd A Wyatt, Tammy Kielian, Peter Oldenburg, Angela M Gleason, Ashley Bauer, Gregory Golden, William W West, Joseph H Sisson, Debra J Romberger
JournalAmerican journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 45 Issue 4 Pg. 711-9 (Oct 2011) ISSN: 1535-4989 [Electronic] United States
PMID21278324 (Publication Type: Journal Article, Research Support, American Recovery and Reinvestment Act, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Bronchoconstrictor Agents
  • Chemokines
  • Cytokines
  • Dust
  • Inflammation Mediators
  • Lipopolysaccharides
  • Peptidoglycan
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Methacholine Chloride
  • Nitric Oxide
Topics
  • Animal Husbandry
  • Animals
  • Bronchial Hyperreactivity (immunology, physiopathology)
  • Bronchoalveolar Lavage Fluid (immunology)
  • Bronchoconstrictor Agents (pharmacology)
  • Chemokines (metabolism)
  • Cytokines (metabolism)
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Dust
  • Housing, Animal
  • Inflammation Mediators (metabolism)
  • Inhalation Exposure
  • Lipopolysaccharides (pharmacology)
  • Lung (drug effects, immunology, physiopathology)
  • Macrophages, Alveolar (immunology)
  • Methacholine Chloride (pharmacology)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophil Infiltration
  • Neutrophils (immunology)
  • Nitric Oxide (metabolism)
  • Peptidoglycan (pharmacology)
  • Pneumonia (chemically induced, immunology, physiopathology, prevention & control)
  • Swine
  • Time Factors
  • Toll-Like Receptor 2 (agonists, deficiency, genetics, metabolism)

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