Allergens induced release of alarmins from airway epithelial cells

Abstract

Background: Airway epithelial cells (AECs) are the first site of interaction with allergens. The mechanisms underlying allergenicity are not fully understood.Allergens can stimulate epithelial and immune cells through protease-activated, or pattern recognition receptors. AECs release alarmins that trigger lung inflammation.Uric acid (UA) and ATP are essential initiators and amplifiers of pulmonary allergy. Allergen-challenged asthmatic patients have increased levels of UA and ATP in the airways (Kool, M. et al. Immunity 2011; 34:527-40 and Idzko, M. et al. Nat Med 2007; 13:913–919).We aimed to study the effects of 4 different common allergens on UA and ATP release, and IL-8 expression in human bronchial epithelial cells. Methods: Bronchial epithelial cells (BEAS-2B) were exposed to various concentrations of house dust mite (HDM), A. alternata, A.vulgaris and B.pendula . Heat-inactivated allergens where used as control for proteolytic activity.Cell culture supernatant and cell lysates were collected and levels of UA, ATP and IL-8 were measured. Results: HDM but no other allergen dose-dependently induced the release of UA at 6h and 24h. This effect was abrogated by heat inactivation. All allergens induced rapid release of ATP,whereas heat-inactivated allergens were without effect. Furthermore, all allergens , dose-dependently increased IL-8 gene and protein expression. IL-8 induction by heat-inactivated extracts was significantly lower than the active form. Conclusion: In our study, aeroallergens increased ATP and IL-8 release from AECs,while only HDM induced the release of UA. The fact that these effects were reduced by heat-inactivation, presumably by reducing proteolytic activity, opens up prospects for therapy.