title: Alveolar macrophages play a key role in cockroach-induced allergic inflammation via TNF-α pathway.
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.
authors.affiliation: Ewha Womans University College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul, South Korea.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Sohn
authors.forename: Je-Min
authors.initials: JM
authors.lastname: Choi
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Chein-Soo
authors.initials: CS
authors.lastname: Hong
authors.forename: Joo-Shil
authors.initials: JS
authors.lastname: Lee
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Park
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020048:Blattellidae / Q000737:chemistry* / Q000201:enzymology; D002460:Cell Line; D045424:Complex Mixtures / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019476:Insect Proteins / Q000276:immunology* / Q000494:pharmacology; D018793:Interleukin-13 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D044464:Receptor, PAR-2 / Q000235:genetics / Q000276:immunology; D057057:Serine Proteases / Q000276:immunology* / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D000485:Allergens; D045424:Complex Mixtures; D019476:Insect Proteins; D018793:Interleukin-13; D015848:Interleukin-5; D044464:Receptor, PAR-2; D015842:Serine Proteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D057057:Serine Proteases