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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptive Immunity / drug effects
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Administration, Intranasal
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Allergens / immunology*
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Allergens / pharmacology
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Animals
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Asthma / chemically induced
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Asthma / immunology*
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Asthma / metabolism
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Asthma / pathology
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Blattellidae / chemistry*
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Blattellidae / enzymology
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Cell Line
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Complex Mixtures / chemistry
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Complex Mixtures / immunology*
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Complex Mixtures / pharmacology
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Gene Expression Regulation / drug effects
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Immunity, Innate / drug effects
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Immunoglobulin E / blood
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Inflammation / chemically induced
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Inflammation / immunology*
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Inflammation / metabolism
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Inflammation / pathology
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Insect Proteins / immunology*
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Insect Proteins / pharmacology
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Interleukin-13 / blood
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Interleukin-5 / blood
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Lung / immunology
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Lung / metabolism
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Lung / pathology
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Macrophages, Alveolar / immunology*
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Macrophages, Alveolar / metabolism
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Macrophages, Alveolar / pathology
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Mice
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Mice, Inbred BALB C
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Receptor, PAR-2 / genetics
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Receptor, PAR-2 / immunology
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Serine Proteases / immunology*
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Serine Proteases / pharmacology
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Serine Proteinase Inhibitors / pharmacology
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Signal Transduction / drug effects
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / immunology*
Substances
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Allergens
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Complex Mixtures
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Insect Proteins
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Interleukin-13
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Interleukin-5
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Receptor, PAR-2
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Serine Proteinase Inhibitors
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Tumor Necrosis Factor-alpha
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Immunoglobulin E
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Serine Proteases
Grants and funding
This study was supported by the grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A092076). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.