Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Antiinflammatory effects of bromodomain and extraterminal domain inhibition in cystic fibrosis lung inflammation
Kong Chen, … , Joseph M. Pilewski, Jay K. Kolls
Kong Chen, … , Joseph M. Pilewski, Jay K. Kolls
Published July 21, 2016
Citation Information: JCI Insight. 2016;1(11):e87168. https://doi.org/10.1172/jci.insight.87168.
View: Text | PDF
Research Article Inflammation Therapeutics

Antiinflammatory effects of bromodomain and extraterminal domain inhibition in cystic fibrosis lung inflammation

  • Text
  • PDF
Abstract

Significant morbidity in cystic fibrosis (CF) results from chronic lung inflammation, most commonly due to Pseudomonas aeruginosa infection. Recent data suggest that IL-17 contributes to pathological inflammation in the setting of abnormal mucosal immunity, and type 17 immunity–driven inflammatory responses may represent a target to block aberrant inflammation in CF. Indeed, transcriptomic analysis of the airway epithelium from CF patients undergoing clinical bronchoscopy revealed upregulation of IL-17 downstream signature genes, implicating a substantial contribution of IL-17–mediated immunity in CF lungs. Bromodomain and extraterminal domain (BET) chromatin modulators can regulate T cell responses, specifically Th17-mediated inflammation, by mechanisms that include bromodomain-dependent inhibition of acetylated histones at the IL17 locus. Here, we show that, in vitro, BET inhibition potently suppressed Th17 cell responses in explanted CF tissue and inhibited IL-17–driven chemokine production in human bronchial epithelial cells. In an acute P. aeruginosa lung infection murine model, BET inhibition decreased inflammation, without exacerbating infection, suggesting that BET inhibition may be a potential therapeutic target in patients with CF.

Authors

Kong Chen, Brian T. Campfield, Sally E. Wenzel, Jeremy P. McAleer, James L. Kreindler, Geoffrey Kurland, Radha Gopal, Ting Wang, Wei Chen, Taylor Eddens, Kathleen M. Quinn, Mike M. Myerburg, William T. Horne, Jose M. Lora, Brian K. Albrecht, Joseph M. Pilewski, Jay K. Kolls

×

Figure 1

Enriched T cell signatures are present in CF epithelium.

Options: View larger image (or click on image) Download as PowerPoint
Enriched T cell signatures are present in CF epithelium.
(A) RNA-seq hea...
(A) RNA-seq heat maps of CF bronchial brushings vs. control bronchial brushings. Th1, Th2, and Th17 gene signatures determined by RNA-seq from RNA obtained from cytokine-stimulated NHBE cells are shown. (B) T cell signatures in bronchial brushings from individual control and CF patients. Donor demographics are summarized in Supplemental Tables 1 and 2.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts