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 potential of bronchial epithelium is affected by its local environment and explored this hypothesis with respect to the effect of IL-9 on bronchial epithelium. We investigated the response of primary and immortalized human bronchial epithelial cells to IL-9 stimulation with respect to the release of T-cell 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 regulated on activation, normal T cells expressed and secreted (RANTES) in a dose-dependent fashion. We found a similar dose response to IL-9 in primary cells from bronchial brushings of healthy subjects and that nearly all of the T-cell chemoattraction was attributable to IL-16 and RANTES. Reverse transcriptase/polymerase chain reaction of BEAS-2B, HBE4-E6/E7, and primary cells 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 HBE4-E6/E7 and primary cells confirmed surface expression of the IL-9 receptor. Costimulation of both cell types with IL-9 and antibody to either gamma-common chain or IL-9Ralpha completely blocked the release of T-cell chemoattractant activity, confirming the primary role of a functioning IL-9 receptor for IL-9 signaling in HBE4-E6/E7 and primary bronchial epithelial cells. 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 response in allergic airway inflammation.
Little
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The Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA. flittle@lung.bumc.bu.edu
Cruikshank
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Center
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D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology; D017077:Culture Media, Conditioned; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D019410:Interleukin-16 / Q000378:metabolism*; D016906:Interleukin-9 / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
D018946:Chemokine CCL5; D017077:Culture Media, Conditioned; D019410:Interleukin-16; D016906:Interleukin-9; D011994:Recombinant Proteins