TFF1 is silenced during chronic Helicobacter pylori infection by IFNgamma

ELETTO, DANIELA; FÁTIMA MARIA MENTUCCI; VOLI, ANTONIA; PORTA, AMALIA; TOSCO, ALESSANDRA

Congreso; 16th SIBBM Seminar .Frontiers in Molecular Biology. Frontiers in metabolic research; 2021

When a foreign stimulus alters the physiological homeostasis, the immune system activatesan acute response with the main purpose of removing the disturbing insult and restoring theinitial conditions. This kind of inflammation is therefore beneficial, although if it persists overtimeand becomes chronic, its role may be detrimental and increase the risk of cancer.Helicobacter pylori-induced gastritis is one of the chronic inflammatory diseasescharacterized by an unregulated inflammation. H. pylori colonization triggers initially theinnate host immune response which recruits macrophages and dendritic cells to the gastricmucosa and activates these cells to secrete cytokines, such as IL-1, IL-6, TNF-α and IFN-γ. Ifthis response fails to eradicate the pathogen, the inflammatory cytokines sustain the mucosalinflammation and contribute to the development of chronic gastritis. In this context, manyfactors are affected by the persistent production of inflammatory cytokines and one of theseis the Trefoil Factor 1 (TFF1). This secreted protein plays a protective role in the humangastric mucosa by maintaining its integrity and hampering H. pylori infection. Indeed, TFF1expression is stimulated by the exposure to the invasive pathogen but gradually silencedunder continuous H. pylori-depending inflammation. In agreement with this evidence, in morethan half of gastric adenocarcinomas TFF1 expression is lost. The molecular mechanismregulating its expression is still unknown and is currently under investigation in our lab. Ourexperiments indicate that IFN-γ plays a role in TFF1 downregulation in gastric cells and,preliminary evidence, suggest that DNA methylation in involved in IFN-γ-dependent silencing.We are currently trying to identify the whole pathway initiated by the stimulation of IFN-γ.