IFN-gamma-enhanced allergen penetration across respiratory epithelium augments allergic inflammation.
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.
Reisinger
Jürgen
J
Department of Otorhinolaryngology, Medical University of Vienna, Austria.
Triendl
Andrea
A
Küchler
Ernst
E
Bohle
Barbara
B
Krauth
Maria Theresa
MT
Rauter
Ingrid
I
Valent
Peter
P
Koenig
Franz
F
Valenta
Rudolf
R
Niederberger
Verena
V
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
D000485:Allergens; D011994:Recombinant Proteins; D006632:Histamine; D007371:Interferon-gamma