Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: Important implications in asthma

Fei Huang, Shinichiro Wachi, Philip Thai, Artem Loukoianov, Kin Hup Tan, Rosanna Malbran Forteza, Reen Wu

Research output: Contribution to journalArticle

68 Scopus citations

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 languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology
Volume121
Issue number6
DOIs
StatePublished - 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

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