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Alveolar macrophages play a key role in cockroach-induced allergic inflammation via TNF-α pathway

Authors
 Joo Young Kim  ;  Jung Ho Sohn  ;  Je-Min Choi  ;  Jae-Hyun Lee  ;  Chein-Soo Hong  ;  Joo-Shil Lee  ;  Jung-Won Park 
Citation
 PLOS ONE, Vol.7(10) : e47971, 2012 
Journal Title
 PLOS ONE 
Issue Date
2012
MeSH
Adaptive Immunity/drug effects ; Administration, Intranasal ; Allergens/immunology* ; Allergens/pharmacology ; Animals ; Asthma/chemically induced ; Asthma/immunology* ; Asthma/metabolism ; Asthma/pathology ; Blattellidae/chemistry* ; Blattellidae/enzymology ; Cell Line ; Complex Mixtures/chemistry ; Complex Mixtures/immunology* ; Complex Mixtures/pharmacology ; Gene Expression Regulation/drug effects ; Immunity, Innate/drug effects ; Immunoglobulin E/blood ; Inflammation/chemically induced ; Inflammation/immunology* ; Inflammation/metabolism ; Inflammation/pathology ; Insect Proteins/immunology* ; Insect Proteins/pharmacology ; Interleukin-13/blood ; Interleukin-5/blood ; Lung/immunology ; Lung/metabolism ; Lung/pathology ; Macrophages, Alveolar/immunology* ; Macrophages, Alveolar/metabolism ; Macrophages, Alveolar/pathology ; Mice ; Mice, Inbred BALB C ; Receptor, PAR-2/genetics ; Receptor, PAR-2/immunology ; Serine Proteases/immunology* ; Serine Proteases/pharmacology ; Serine Proteinase Inhibitors/pharmacology ; Signal Transduction/drug effects ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/immunology*
Keywords
Adaptive Immunity/drug effects ; Administration, Intranasal ; Allergens/immunology* ; Allergens/pharmacology ; Animals ; Asthma/chemically induced ; Asthma/immunology* ; Asthma/metabolism ; Asthma/pathology ; Blattellidae/chemistry* ; Blattellidae/enzymology ; Cell Line ; Complex Mixtures/chemistry ; Complex Mixtures/immunology* ; Complex Mixtures/pharmacology ; Gene Expression Regulation/drug effects ; Immunity, Innate/drug effects ; Immunoglobulin E/blood ; Inflammation/chemically induced ; Inflammation/immunology* ; Inflammation/metabolism ; Inflammation/pathology ; Insect Proteins/immunology* ; Insect Proteins/pharmacology ; Interleukin-13/blood ; Interleukin-5/blood ; Lung/immunology ; Lung/metabolism ; Lung/pathology ; Macrophages, Alveolar/immunology* ; Macrophages, Alveolar/metabolism ; Macrophages, Alveolar/pathology ; Mice ; Mice, Inbred BALB C ; Receptor, PAR-2/genetics ; Receptor, PAR-2/immunology ; Serine Proteases/immunology* ; Serine Proteases/pharmacology ; Serine Proteinase Inhibitors/pharmacology ; Signal Transduction/drug effects ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/immunology*
Abstract
The activity of the serine protease in the German cockroach allergen is important to the development of allergic disease. The protease-activated receptor (PAR)-2, which is expressed in numerous cell types in lung tissue, is known to mediate the cellular events caused by inhaled serine protease. Alveolar macrophages express PAR-2 and produce considerable amounts of tumor necrosis factor (TNF)-α. We determined whether the serine protease in German cockroach extract (GCE) enhances TNF-α production by alveolar macrophages through the PAR-2 pathway and whether the TNF-α production affects GCE-induced pulmonary inflammation. Effects of GCE on alveolar macrophages and TNF-α production were evaluated using in vitro MH-S and RAW264.6 cells and in vivo GCE-induced asthma models of BALB/c mice. GCE contained a large amount of serine protease. In the MH-S and RAW264.7 cells, GCE activated PAR-2 and thereby produced TNF-α. In the GCE-induced asthma model, intranasal administration of GCE increased airway hyperresponsiveness (AHR), inflammatory cell infiltration, productions of serum immunoglobulin E, interleukin (IL)-5, IL-13 and TNF-α production in alveolar macrophages. Blockade of serine proteases prevented the development of GCE induced allergic pathologies. TNF-α blockade also prevented the development of such asthma-like lesions. Depletion of alveolar macrophages reduced AHR and intracellular TNF-α level in pulmonary cell populations in the GCE-induced asthma model. These results suggest that serine protease from GCE affects asthma through an alveolar macrophage and TNF-α dependent manner, reflecting the close relation of innate and adaptive immune response in allergic asthma model.
Files in This Item:
T201203714.pdf Download
DOI
23094102
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Park, Jung Won(박중원) ORCID logo https://orcid.org/0000-0003-0249-8749
Sohn, Jung Ho(손정호)
Lee, Jae Hyun(이재현) ORCID logo https://orcid.org/0000-0002-0760-0071
Hong, Chein Soo(홍천수)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91721
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