A Role for RUNX3 in Inflammation-Induced Expression of IL23A in Gastric Epithelial Cells

Yit Teng Hor; Dominic Chih-Cheng Voon; Jason Kin Wai Koo; Huajing Wang; Wen Min Lau; Hassan Ashktorab; Shing Leng Chan; Yoshiaki Ito

A Role for RUNX3 in Inflammation-Induced Expression of IL23A in Gastric Epithelial Cells

2014

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).

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