title: House dust mite allergen Der p 1 elevates the release of inflammatory cytokines and expression of adhesion molecules in co-culture of human eosinophils and bronchial epithelial cells.
abstract: House dust mite (HDM) is a common allergen of allergic asthma. Eosinophils are principal effector cells of allergic inflammation and their adhesion onto human bronchial epithelial cells is mediated by a CD18-intracellular adhesion molecule-1 (ICAM-1)-dependent interaction. We studied the effects of HDM Dermatophagoides pteronyssinus (Der p) 1 on the activation of eosinophils and bronchial epithelial BEAS-2B cells. Cytokines and adhesion molecules were measured using flow cytometry. Transcription factor nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) and signaling molecule p38 mitogen-activated protein kinase (MAPK) were analyzed using electromobility shift assay and western blot, respectively. Der p 1 protein was found to potently induce the release of IL-1beta, IL-6, IL-10, tumor necrosis factor (TNF)-alpha and granulocyte macrophage colony-stimulating factor from eosinophils. Such induction was further up-regulated for IL-6 and IL-10, and down-regulated for TNF-alpha and IL-1beta in eosinophil-BEAS-2B cells co-culture. Surface expression of CD18 and ICAM-1 on eosinophils was greatly increased by Der p 1; such inductive effect on ICAM-1 was also found to be more prominent on BEAS-2B cells from the co-culture than BEAS-2B cells alone. Der p 1 was found to activate NF-kappaB and AP-1 activity in eosinophils alone and in co-culture and BEAS-2B cells in co-culture. Moreover, Der p 1 could activate p38 MAPK in BEAS-2B cells and eosinophils alone and in co-culture. Selective inhibition of NF-kappaB, AP-1 and p38 MAPK resulted in differential suppression of the Der p 1-induced cytokine release and adhesion molecule expression. As an allergen, HDM could therefore induce the release of inflammatory cytokines and expression of adhesion molecules from the interaction of human eosinophils and bronchial epithelial cells.
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.
authors.forename: Chun K
authors.initials: CK
authors.lastname: Wong
authors.forename: Mandy L Y
authors.initials: ML
authors.lastname: Li
authors.forename: Cheng B
authors.initials: CB
authors.lastname: Wang
authors.forename: Wai K
authors.initials: WK
authors.lastname: Ip
authors.forename: Ya P
authors.initials: YP
authors.lastname: Tian
authors.forename: Christopher W K
authors.initials: CW
authors.lastname: Lam
mesh_terms: D039741:Antigens, Dermatophagoides / Q000276:immunology*; D060829:Arthropod Proteins; D001249:Asthma / Q000201:enzymology / Q000276:immunology; D001980:Bronchi / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D018920:Coculture Techniques; D003474:Curcumin / Q000378:metabolism / Q000494:pharmacology; D003546:Cysteine Endopeptidases; D016207:Cytokines / Q000276:immunology*; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D004789:Enzyme Activation; D004804:Eosinophils / Q000201:enzymology / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D039981:Pyroglyphidae / Q000145:classification*; D013450:Sulfones / Q000494:pharmacology; D018418:Th2 Cells / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000276:immunology / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D015815:Cell Adhesion Molecules; D016207:Cytokines; D007093:Imidazoles; D016328:NF-kappa B; D009570:Nitriles; D011725:Pyridines; D013450:Sulfones; D018808:Transcription Factor AP-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D048051:p38 Mitogen-Activated Protein Kinases; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1; D003474:Curcumin; C093642:SB 203580