The protease allergen Pen c 13 induces allergic airway inflammation and changes in epithelial barrier integrity and function in a murine model
Journal
Journal of Biological Chemistry
Journal Volume
286
Journal Issue
30
Pages
26667-26679
Date Issued
2011
Author(s)
Abstract
Fungal allergens are associated with the development of asthma, and some have been characterized as proteases. Here, we established an animal model of allergic airway inflammation in response to continuous exposure to proteolytically active Pen c 13, a major allergen secreted by Penicillium citrinum. In functional analyses, Pen c 13 exposure led to increased airway hyperresponsiveness, significant inflammatory cell infiltration, mucus overproduction, and collagen deposition in the lung, dramatically elevated serum levels of total IgE and Pen c 13-specific IgE and IgG1, and increased production of the Th2 cytokines IL-4, IL-5, and IL-13 by splenocytes stimulated in vitro with Pen c 13. To examine the mechanisms involved in the regulation of allergenicity by Pen c 13, we performed two-dimensional fluorescence difference gel electrophoresis analysis combined with nano-LC-MS/MS, followed by bioinformatics analysis to identify potential targets that associated with allergic inflammation, which suggested that galectin-3 and laminin might be involved in novel pathogenic mechanisms. Finally, we focused on junctional proteins between cells, because, in addition to opening of the epithelial barrier by environmental proteases possibly being the initial step in the development of asthma, these proteins are also associated with actin rearrangement. Taken together, our findings indicate that Pen c 13 exposure causes junctional structure alterations and actin cytoskeletal rearrangements, resulting in increased permeability and airway structural changes. These effects probably change the lung microenvironment and foster the development of allergic sensitization. ? 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
SDGs
Other Subjects
Airway inflammation; Allergenicity; Allergic inflammation; Animal model; Bioinformatics analysis; Collagen deposition; Continuous exposure; Cytokines; Cytoskeletal rearrangements; Epithelial barrier; Gel electrophoresis analysis; In-vitro; Inflammatory cells; Laminin; Major allergens; Microenvironments; Murine model; Nano-LC-MS; Pathogenic mechanisms; Penicillium citrinum; Serum levels; Splenocytes; Structural change; Allergies; Bioinformatics; Biological organs; Body fluids; Diseases; Electrophoresis; Enzyme activity; Pathology; Proteins; actin; allergen; cell protein; collagen; cytokine; galectin 3; immunoglobulin E; immunoglobulin G1; interleukin 13; interleukin 4; interleukin 5; laminin; protein Pen c 13; serine proteinase; unclassified drug; allergenicity; allergic asthma; animal cell; animal experiment; animal model; animal tissue; article; bioinformatics; cell function; cell infiltration; cell membrane permeability; cell stimulation; controlled study; cytokine production; experimental model; female; human; human cell; immunoglobulin blood level; in vitro study; inflammatory cell; liquid chromatography; mass spectrometry; molecular mechanics; mouse; nonhuman; pathogenesis; Penicillium citrinum; priority journal; protein degradation; protein secretion; respiratory epithelium; respiratory tract allergy; respiratory tract inflammation; spleen cell; Th2 cell; two dimensional difference gel electrophoresis; Allergens; Animals; Antigens, Fungal; Asthma; Cytokines; Cytoskeleton; Disease Models, Animal; Female; Fungal Proteins; Galectin 3; Humans; Immunoglobulin E; Immunoglobulin G; Laminin; Lung; Mice; Mice, Inbred BALB C; Microfilaments; Penicillium; Peptide Hydrolases; Respiratory Mucosa; Th2 Cells; Animalia; Murinae; Penicillium citrinum
Type
journal article