Alveolar Macrophages Play a Key Role in Cockroach-Induced Allergic Inflammation via TNF-alpha Pathway

Title
Alveolar Macrophages Play a Key Role in Cockroach-Induced Allergic Inflammation via TNF-alpha Pathway
Author
최제민
Keywords
PROTEASE-ACTIVATED RECEPTOR-2; AIRWAY EPITHELIAL-CELLS; INNATE IMMUNE-RESPONSEAlveolar Macrophages Play a Key Role in; GERMAN-COCKROACH; DUST-MITE; IL-8 EXPRESSION; LUNG-DISEASE; ASTHMA; EXPOSURE; SENSITIZATION
Issue Date
2012-10
Publisher
PUBLIC LIBRARY SCIENCE, 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
Citation
PLOS ONE, Vol.7, No.10 [2012], p1-12
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)-alpha. We determined whether the serine protease in German cockroach extract (GCE) enhances TNF-alpha production by alveolar macrophages through the PAR-2 pathway and whether the TNF-alpha production affects GCE-induced pulmonary inflammation. Effects of GCE on alveolar macrophages and TNF-alpha 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-alpha. 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-alpha production in alveolar macrophages. Blockade of serine proteases prevented the development of GCE induced allergic pathologies. TNF-alpha blockade also prevented the development of such asthma-like lesions. Depletion of alveolar macrophages reduced AHR and intracellular TNF-alpha 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-alpha dependent manner, reflecting the close relation of innate and adaptive immune response in allergic asthma model.
URI
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0047971http://hdl.handle.net/20.500.11754/40039
ISSN
1932-6203
DOI
10.1371/journal.pone.0047971
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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