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Cell Rep. 2014 Jul 10;8(1):50-8. doi: 10.1016/j.celrep.2014.06.003. Epub 2014 Jul 5.

A role for RUNX3 in inflammation-induced expression of IL23A in gastric epithelial cells.

Author information

  • 1Cancer Stem Cells and Biology Programme, Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456, Singapore.
  • 2Cancer Stem Cells and Biology Programme, Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
  • 3Cancer Center and Gastroenterology Division, Department of Medicine, Howard University Hospital, 2041 Georgia Avenue N.W., Washington, DC 20060, USA.
  • 4Cancer Stem Cells and Biology Programme, Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore. Electronic address: csiitoy@nus.edu.sg.

Abstract

RUNX3 functions as a tumor suppressor in the gastric epithelium, where its inactivation is frequently observed during carcinogenesis. We identified IL23A as a RUNX3 target gene in gastric epithelial cells. This was confirmed in a series of in vitro analyses in gastric epithelial cell lines. In elucidating the underlying regulatory network, we uncovered a prominent role for the TNF-α/NF-κB pathway in activating IL23A transcription. Moreover, the activating effect of TNF-α was markedly augmented by the infection of Helicobacter pylori, the primary cause of human gastritis. Of note, H. pylori utilized the CagA/SHP2 pathway to activate IL23A, as well as the induction of the NOD1 pathway by iE-DAP. Importantly, RUNX3 synergized strongly with these physiologically relevant stimuli to induce IL23A. Lastly, we present evidence for the secretion of IL23A by gastric epithelial cells in a form that is distinct from canonical IL-23 (IL23A/IL12B).

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

PMID:
25008775
[PubMed - in process]
PMCID:
PMC4307917
[Available on 2015-07-10]
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