Activation of Signal Transduction and Activator of Transcription 3 Signaling Contributes to -Associated Gastric Epithelial Proliferation and Inflammation.

Background/aim: Although IL-6-mediated activation of the signal transduction and activator of transcription 3 (STAT3) axis is involved in inflammation and cancer, the role of STAT3 in -associated gastric inflammation and carcinogenesis is unclear. This study investigated the role of STAT3 in gastric inflammation and carcinogenesis and examined the molecular mechanism of -induced gastric phenotypes.

Methods: To evaluate the contribution of STAT3 to gastric inflammation and carcinogenesis, we used wild-type (WT) and gastric epithelial conditional -knockout ( ) mice. Mice were infected with and euthanized at 18 months postinfection. Mouse gastric organoids were treated with recombinant IL-6 (rIL-6) or rIL-11 and a JAK inhibitor (JAKi) to assess the role of IL-6/STAT3 signaling .

Results: Inflammation and mucous metaplasia were more severe in WT mice than in mice. The epithelial cell proliferation rate and STAT3 activation were increased in WT mice. Application of rIL-6 and rIL-11 induced expression of intestinal metaplasia-associated genes, such as ; this induction was suppressed by JAKi administration.

Conclusions: Loss of STAT3 signaling in the gastric mucosa leads to decreased epithelial cell proliferation, atrophy, and metaplasia in the setting of infection. Therefore, activation of STAT3 signaling may play a key role in -associated gastric carcinogenesis.