IL-9 stimulates release of chemotactic factors from human bronchial epithelial cells

Interleukin (IL)-9 is a T helper 2 cytokine implicated as a candidate gene and contributor to human asthma. We hypothesized that the inflammatory pote ntial of bronchial epithelium is affected by its local environment and expl ored this hypothesis with respect to the effect of IL-9 on bronchial epithe lium. We investigated the response of primary and immortalized human bronch ial epithelial cells to IL-9 stimulation with respect to the release of T-c ell chemoattractant factors. In response to IL-9, the HBE4-E6/E7 cell line, but not BEAS-2B cells, released the T-cell chemoattractants IL-16 and regu lated on activation, normal T cells expressed and secreted (RANTES) in a do se-dependent fashion. We found a similar dose response to IL-9 in primary c ells from bronchial brushings of healthy subjects and that nearly all of th e T-cell chemoattraction was attributable to IL-16 and RANTES. Reverse tran scriptase/polymerase chain reaction of BEAS-2B, HBE4-E6/E7, and primary cel ls from two subjects revealed messenger RNA for IL-9 receptor (IL-9R) alpha but not in BEAS-2B cells. Fluorescence-activated cell sorter analysis of H BE4-E6/E7 and primary cells confirmed surface expression of the IL-9 recept or. Costimulation of both cell types with IL-9 and antibody to either gamma -common chain or IL-9R alpha completely blocked the release of T-cell chem oattractant activity, confirming the primary role of a functioning IL-9 rec eptor for IL-9 signaling in HBE4-E6/E7 and primary bronchial epithelial cel ls. We conclude that IL-9 is a stimulus for airway epithelial cell release of T-cell chemoattractant factors, which in turn may modulate the immune re sponse in allergic airway inflammation.