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Stimulation of Cytokine Expression in Human Airway Epithelial Cells by IL‐17A: Polarity of Receptor Distribution and Dependence on PI3 Kinase/NF‐κB Signaling Pathways
Author(s) -
Huang Fei,
Kao ChengYuan,
Wachi Shinichiro,
Tai Philip,
Chen Yin,
Ann David Kong,
Wu Reen
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1094-a
Subject(s) - signal transduction , microbiology and biotechnology , ly294002 , biology , pi3k/akt/mtor pathway , respiratory epithelium , ccl20 , cytokine , phosphoinositide 3 kinase , nf κb , epithelium , inflammation , immunology , chemokine , genetics , chemokine receptor
The pro‐inflammatory effects of IL‐17A on airway epithelial cells have been recognized. In order to elucidate the signaling of IL‐17A in the airway, primary human tracheobronchial epithelial cells (TBE) and HBE1 cell line were cultured under an air‐liquid biphasic condition. Differential gene expression was determined by Affymetrix gene chips. We have observed gene induction of IL‐19, GRO‐α, ‐β, ‐γ, CXCL‐5 and GCP‐2 by IL‐17A in addition to those in previous studies, such as HBD2, CCL20, and mucin genes, which were further confirmed by Q‐PCR. Polarity of the treatment and anti‐IL‐17 receptor A (IL‐17AR) antibody staining consistently showed the localization preference of IL‐17AR is at the basal‐lateral side of the epithelium. Inhibitor studies demonstrated that the gene induction is sensitive to the inhibition of PI3K and NF‐κB activation. This is further supported by protein analysis, nuclear translocation and HBD‐2 promoter analysis. However, PI3K inhibitor (LY294002) has no effects on NF‐κB translocation, suggesting an additional PI3K‐independent event is involved in coordinating the NF‐κB‐based transcriptional regulation. Based on these results, IL‐17A basal‐laterally acts through the IL‐17 AR of the polarized airway epithelium to exert the activation of PI3 kinase signaling and NF‐κB translocation to activate the expression of various cytokines.