Abstract
Background: IL-17A and IL-19 are highly expressed in chronic inflammatory diseases, such as psoriasis and asthma. IL-19 plays a significant role in the enhancement of TH2 cytokine secretion in allergic diseases, but its cellular source in asthmatic patients remains unknown. Objective: Our aims were to determine whether the epithelium is a major source of airway mucosal IL-19 and to elucidate the mechanism of gene expression regulation. Methods: Immunofluorescent staining was used to determine IL-19 protein expression in tracheal tissue sections of various airway diseases. Well-differentiated primary human bronchial epithelial cultures and a corresponding cell line were used as in vitro models to study gene regulation. Results: We found significantly higher IL-19 expression in airway epithelia of asthmatic patients than in epithelia of patients with other diseases. Using a cytokine panel, we demonstrated the upregulation of IL-19 expression in cultures by two TH2 cytokines, IL-4 and IL-13, in addition to the previously found TH17 cytokine IL-17A. Moreover, cotreatment of IL-17A and IL-4/IL-13 synergistically upregulated IL-19 expression. Using siRNA and chemical inhibitor approaches, we demonstrated a transcriptional regulation of IL-19 by nuclear factor κB and signal transducer and activator of transcription (STAT) 6. The addition of IL-13 to IL-17A stimulation triggers a shift from nuclear factor κB-dependent transcriptional regulation to one that is STAT6 based. Using chromatin immunoprecipitation assays, we demonstrated the presence of STAT6-binding elements in the IL-19 promoter region. Conclusion: We propose that an IL-17A- and IL-13-induced synergism in IL-19 stimulation in airway epithelia occurs through a STAT6-dependent pathway.
Original language | English (US) |
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Pages (from-to) | 1415-1421.e3 |
Journal | Journal of Allergy and Clinical Immunology |
Volume | 121 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2008 |
Keywords
- airway epithelium
- asthma
- IL-13
- IL-17A
- IL-19
- IL-4
- nuclear factor κB
- signal transducer and activator of transcription 6
- T2 cytokine
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology