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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  ;  Jung-Won Park  ;  Joo-Shil Lee  ;  Chein-Soo Hong  ;  Jae-Hyun Lee  ;  Je-Min Choi 
Citation
 PLoS One, Vol.7(10) : e47971, 2012 
Journal Title
 PLoS One 
ISSN
 1932-6203 
Issue Date
2012
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.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91721
DOI
10.1371/journal.pone.0047971
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
Yonsei Authors
박중원(Park, Jung Won) ; 손정호(Sohn, Jung Ho) ; 이재현(Lee, Jae Hyun) ; 홍천수(Hong, Chein Soo)
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