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Interferon-γ is increased in the gut of patients with irritable bowel syndrome and modulates serotonin metabolism.
Barbaro, Maria Raffaella; Di Sabatino, Antonio; Cremon, Cesare; Giuffrida, Paolo; Fiorentino, Michelangelo; Altimari, Annalisa; Bellacosa, Lara; Stanghellini, Vincenzo; Barbara, Giovanni.
Afiliação
  • Barbaro MR; Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Bologna, Italy;
  • Di Sabatino A; First Department of Internal Medicine, S. Matteo Hospital Foundation, University of Pavia, Pavia, Italy;
  • Cremon C; Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Bologna, Italy;
  • Giuffrida P; First Department of Internal Medicine, S. Matteo Hospital Foundation, University of Pavia, Pavia, Italy;
  • Fiorentino M; Department of Hematology, Oncology and Laboratory Medicine, University of Bologna, Bologna, Italy.
  • Altimari A; Department of Hematology, Oncology and Laboratory Medicine, University of Bologna, Bologna, Italy.
  • Bellacosa L; Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Bologna, Italy;
  • Stanghellini V; Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Bologna, Italy;
  • Barbara G; Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), University of Bologna, Bologna, Italy; giovanni.barbara@unibo.it.
Am J Physiol Gastrointest Liver Physiol ; 310(6): G439-47, 2016 Mar 15.
Article em En | MEDLINE | ID: mdl-26744473
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Serotonina / Interferon gama / Trato Gastrointestinal / Síndrome do Intestino Irritável Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Serotonina / Interferon gama / Trato Gastrointestinal / Síndrome do Intestino Irritável Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2016 Tipo de documento: Article