title: The non-proteolytic house dust mite allergen Der p 2 induce NF-kappaB and MAPK dependent activation of bronchial epithelial cells.
abstract: BACKGROUND
  House dust mites (HDM) are well-known as a source of indoor aeroallergens and for causing allergic airway diseases. Some proteolytic HDM allergens are known to activate respiratory epithelial cells to produce pro-inflammatory mediators, while there is limited knowledge regarding such activity among non-proteolytic HDM allergens.
  
  
  OBJECTIVE
  To investigate whether Der p 2, a major non-proteolytic allergen of Dermatophagoides pteronyssinus, activates respiratory epithelial cells to produce mediators involved in asthma pathogenesis and to elucidate the mechanism of such activation.
  
  
  METHODS
  The human bronchial epithelial cell line BEAS-2B, normal human bronchial epithelial (NHBE) cells and the alveolar epithelial cell line A549 were exposed to recombinant Der p 2. Following exposure, we analysed a panel of soluble mediators and cell adhesion receptors involved in asthma pathogenesis by promoting recruitment, survival and binding of inflammatory cells. The involvement of nuclear factor (NF)-kappaB and mitogen-activated protein kinases (MAPKs) was studied using specific inhibitors.
  
  
  RESULTS
  Der p 2 activated bronchial BEAS-2B and NHBE cells, but not alveolar A549 cells. In BEAS-2B cells Der p 2 induced dose-dependent up-regulation in both mRNA level and protein secretion of granulocyte-macrophage colony-stimulating factor, IL-6, IL-8, monocyte-chemotactic protein-1 and macrophage inflammatory protein-3alpha. Secretion as well as surface expression of intercellular adhesion molecule (ICAM)-1 was also up-regulated, which was associated with increased adhesion of monocytes to the epithelial cells. The release of cytokines and chemokines was regulated by NF-kappaB and MAPK activation in different ways, while expression of ICAM-1 was solely dependent on NF-kappaB activation.
  
  
  CONCLUSIONS
  These results show that Der p 2 activates respiratory epithelial cells, indicating that this non-proteolytic allergen, in addition to its immunogenic properties, can aggravate respiratory airway disease by adjuvant-like activation of the lung epithelium.
authors.affiliation: Swedish Defence Research Agency, FOI CBRN Defence and Security, Umeå, Sweden. camilla.osterlund@foi.se
authors.forename: C
authors.initials: C
authors.lastname: Osterlund
authors.forename: H
authors.initials: H
authors.lastname: Grönlund
authors.forename: N
authors.initials: N
authors.lastname: Polovic
authors.forename: S
authors.initials: S
authors.lastname: Sundström
authors.forename: G
authors.initials: G
authors.lastname: Gafvelin
authors.forename: A
authors.initials: A
authors.lastname: Bucht
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D060829:Arthropod Proteins; D001249:Asthma / Q000276:immunology / Q000503:physiopathology; D001980:Bronchi / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054418:Chemokine CCL20 / Q000378:metabolism; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D012333:RNA, Messenger / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D018932:Chemokine CCL2; D054418:Chemokine CCL20; C451163:Dermatophagoides pteronyssinus antigen p 2; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020928:Mitogen-Activated Protein Kinases