IL‐6 Production in Human Bronchial Epithelial Cells in Response to House Dust Mite Allergen

Abstract

Airway epithelial cells lie at the interface between host and environment, representing the first line of defense against pathogens. In addition to its role as protective barrier, the airway epithelium can activate underlying dendritic cells, thereby initiating and prolonging airway inflammation. Furthermore, alterations in epithelial ion transport mechanisms can modify many aspects of its signaling, mucus properties, bacterial defenses, and induction of immunity. IL‐6 is a proinflammatory cytokine produced mainly by the innate immune system and is increased in many pulmonary diseases, but its role(s) remain unclear. The objective of our research is to determine the mechanism(s) by which the airway epithelium drives the immunopathology of allergic asthma and to clarify the relationship(s) between the epithelium and IL‐6 in asthma pathogenesis. Normal Human Bronchial Epithelial (Lonza) were grown on collagen‐coated transwell inserts and cultured at ALI until full differentiation (~20 d, TER ~500 Ω), and subsequently treated with house dust mite allergen (HDM, 50 or 100 ug/mL; Greer) for 24 h. IL‐6 production was measured via ELISA (R&D), and increased in dose‐dependent manner after HDM treatment (50 ug/ml HDM: 878±235 pg/mL, or 142% increase, and for 100 ug/mL of HDM:1325±18.7 pg/mL, or 215% increase, p=0.04) compared to sham treatment (618±433 pg/mL). Our data indicate that bronchial epithelial cells may drive allergic asthma via IL‐6 production. Our ongoing studies seek to determine the relationship(s) between the airway epithelium, IL‐6 production, and other aspects of epithelial dysfunction in asthma pathogenesis, including dysregulated mucus production and epithelial ion transport.