Interferon-γ is increased in the gut of patients with irritable bowel syndrome and modulates serotonin metabolism

Maria R affaella Barbaro, Antonio Di Sabatino, Cesare Cremon, Paolo Giuffrida, Michelangelo Fiorentino, Annalisa Altimari, Lara Bellacosa, Vincenzo Stanghellini, Giovanni Barbara

Research output: Contribution to journalArticlepeer-review

Abstract

Mucosal immune activation and altered serotonin metabolism participate in the pathophysiology of irritable bowel syndrome (IBS). However, the reciprocal interplay between these two systems remains unknown. We evaluated the expression and release of interferon (IFN)-γ from the colonic mucosa of patients with IBS and its impact on serotonin reuptake transporter (SERT) gene expression in Caco-2 cells. qPCR was used to evaluate IFN-γ gene expression in colonic mucosal biopsies, whereas IFN-γ protein amount was assessed by ELISA. Colonic T box expressed in T cells (T-bet) and phosphorylated signal transducer and activator of transcription 4 protein amount were evaluated by Western blot. The impact of colonic mucosal mediators on SERT gene expression was evaluated in Caco-2 cells using qPCR. IFN-γ receptor was silenced in Caco-2 cells to determine the effect of IFN-γ released by mucosal biopsies. Compared with asymptomatic controls (ACs), the expression of IFN-γ gene and its transcription factor T-bet were markedly increased in the colonic mucosa of patients with IBS. Compared with ACs, IFN-γ protein tissue levels and its release by mucosal biopsies were significantly increased in IBS. The exposure of Caco-2 cells to IBS supernatants induced a significant decrease in SERT gene expression, independently of IBS subtypes, compared with AC mucosal supernatants. In Caco-2 cells, IFN-γ receptor silencing reversed the reduction of SERT expression evoked by IBS supernatants vs. nonsilenced cell lines. IFN-γ gene, its transcription factor T-bet, IFN-γ protein expression, and its release are increased in the colonic mucosa of patients with IBS and downregulate SERT gene expression in vitro. These results suggest that IFN-γ downregulates SERT expression, hence likely playing a role in altered serotonin metabolism of patients with IBS.

Original languageEnglish
Pages (from-to)G439-G447
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume310
Issue number6
DOIs
Publication statusPublished - Mar 15 2016

Keywords

  • gut mucosa
  • interferon-γ
  • irritable bowel syndrome
  • serotonin reuptake transporter
  • T box expressed in T cells

ASJC Scopus subject areas

  • Medicine(all)

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