title: IFN-gamma-enhanced allergen penetration across respiratory epithelium augments allergic inflammation.
abstract: BACKGROUND
  Respiratory allergen contact is the critical event in the elicitation and boosting of allergen-specific immune responses, as well as in the induction of immediate and late inflammatory reactions.
  
  
  OBJECTIVE
  We sought to investigate the influence of various factors of allergic inflammation on the integrity and barrier function of respiratory epithelium for allergens.
  
  
  METHODS
  We cultured the human bronchial epithelial cell line 16HBE14o- in a transwell culture system as a surrogate of intact respiratory epithelium and used purified iodine 125-labeled recombinant major birch pollen allergen (rBet v 1) to study the extent, kinetics, and factors influencing transepithelial allergen penetration.
  
  
  RESULTS
  Culture supernatants from activated allergen-specific T H 1 clones decreased transepithelial resistance. A screening of various factors (histamine, IFN-gamma, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-8, IL-12, and TNF-alpha) identified IFN-gamma as a potent factor capable of reducing epithelial barrier properties and enhancing transepithelial allergen penetration. Increased submucosal allergen concentrations caused by IFN-gamma-mediated reduction of epithelial barrier function provoked a more than 7-fold augmentation of histamine release from sensitized basophils.
  
  
  CONCLUSIONS
  These results demonstrate that the T H 1 cell-derived cytokine IFN-gamma facilitates allergen penetration through the respiratory epithelium and thereby can aggravate allergic inflammation.
authors.affiliation: Department of Otorhinolaryngology, Medical University of Vienna, Austria.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Reisinger
authors.forename: Andrea
authors.initials: A
authors.lastname: Triendl
authors.forename: Ernst
authors.initials: E
authors.lastname: Küchler
authors.forename: Barbara
authors.initials: B
authors.lastname: Bohle
authors.forename: Maria Theresa
authors.initials: MT
authors.lastname: Krauth
authors.forename: Ingrid
authors.initials: I
authors.lastname: Rauter
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.forename: Franz
authors.initials: F
authors.lastname: Koenig
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
authors.forename: Verena
authors.initials: V
authors.lastname: Niederberger
mesh_terms: D000485:Allergens / Q000378:metabolism*; D001491:Basophils / Q000187:drug effects / Q000378:metabolism; D029662:Betula / Q000276:immunology; D001692:Biological Transport / Q000187:drug effects; D001980:Bronchi; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology*; D011058:Pollen / Q000276:immunology; D011994:Recombinant Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D013997:Time Factors
chemical_list: D000485:Allergens; D011994:Recombinant Proteins; D006632:Histamine; D007371:Interferon-gamma