Document Detail


Elevated amount of Toll-like receptor 4 mRNA in bronchial epithelial cells is associated with airway inflammation in horses with recurrent airway obstruction.
MedLine Citation:
PMID:  17158595     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recurrent airway obstruction (RAO) is characterized by neutrophilic airway inflammation and obstruction, and stabling of susceptible horses triggers acute disease exacerbations. Stable dust is rich in endotoxin, which is recognized by Toll-like receptor (TLR) 4. In human bronchial epithelium, TLR4 stimulation leads to elevation of interleukin (IL)-8 mRNA expression. The zinc finger protein A20 negatively regulates this pathway. We hypothesized that TLR4 and IL-8 mRNA and neutrophil numbers are elevated and that A20 mRNA is not increased in RAOs during stabling compared with controls and with RAOs on pasture. We measured the maximal change in pleural pressure (DeltaPpl(max)), determined inflammatory cell counts in bronchoalveolar lavage fluid (BAL), and quantified TLR4, IL-8, and A20 mRNA in bronchial epithelium by quantitative RT-PCR. We studied six horse pairs, each pair consisting of one RAO and one control horse. Each pair was studied when the RAO-affected horse had airway obstruction induced by stabling and after 7, 14, and 28 days on pasture. Stabling increased BAL neutrophils, DeltaPpl(max), and TLR4 (4.14-fold change) significantly in RAOs compared with controls and with RAOs on pasture. TLR4 correlated with IL-8 (R2 = 0.75). Whereas stabling increased IL-8 in all horses, A20 was unaffected. IL-8 was positively correlated with BAL neutrophils (R2 = 0.43) and negatively with A20 (R2 = 0.44) only in RAO-affected horses. Elevated TLR4 expression and lack of A20 upregulation in bronchial epithelial cells from RAO-affected horses may contribute to elevated IL-8 production, leading to exaggerated neutrophilic airway inflammation in response to inhalation of stable dust.
Authors:
Annerose Berndt; Frederik J Derksen; Patrick J Venta; Susan Ewart; Vilma Yuzbasiyan-Gurkan; N Edward Robinson
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Publication Detail:
Type:  Journal Article     Date:  2006-12-08
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  292     ISSN:  1040-0605     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-12     Completed Date:  2007-05-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L936-43     Citation Subset:  IM    
Affiliation:
Pulmonary Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University East Lansing, MI 48824, USA. berndtan@cvm.msu.edu
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MeSH Terms
Descriptor/Qualifier:
Airway Obstruction / physiopathology,  veterinary*
Animals
Bronchi / cytology,  metabolism*
Bronchoalveolar Lavage Fluid / cytology
Dust
Epithelial Cells / metabolism
Female
Horse Diseases / physiopathology*
Horses
Housing, Animal
Inflammation / etiology,  veterinary
Interleukin-8 / biosynthesis
Male
RNA, Messenger / metabolism
Respiratory Function Tests / veterinary
Toll-Like Receptor 4 / genetics*
Chemical
Reg. No./Substance:
0/Dust; 0/Interleukin-8; 0/RNA, Messenger; 0/Toll-Like Receptor 4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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