title: Signal transducers and activators of transcription 3 signaling pathway: an essential mediator of inflammatory bowel disease and other forms of intestinal inflammation.
abstract: Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of chronic inflammatory bowel disease (IBD), are characterized by mucosal immune cell activation that is driven by a cytokine imbalance. Several cytokines involved in IBD act through the activation of the signal transducers and activators of transcription (STAT) family. We investigated the activation of STAT3 in the mucosa of CD and UC patients, and evaluated whether this event is specific for IBD patients. Using immunofluorescence and immunoblotting, total and phosphorylated STAT3 levels were assessed in biopsy specimens, isolated lamina propria mononuclear cells, and peripheral blood mononuclear cells from patients with CD, UC, other forms of intestinal inflammation, and control subjects. Immunoblotting revealed phosphorylated STAT3 in mucosal biopsy specimens from patients with CD, UC, celiac disease, and acute self-limited colitis, but not in the normal mucosa of control subjects. In IBD patients, STAT3 activation was confined to actively inflamed areas. Accordingly, activated STAT3 was detected in isolated lamina propria mononuclear cells from inflamed IBD tissues, but not in peripheral blood mononuclear cells from control subjects or IBD patients. Immunofluorescence demonstrated that the sources of activated STAT3 were macrophages and T lymphocytes, but not neutrophils. STAT3 activation also was detected in T cells infiltrating the duodenal mucosa of celiac disease patients. We conclude that STAT3 signaling occurs in both CD and UC, where it is strictly confined to areas of active inflammation and is limited to infiltrating macrophages and T cells. The occurrence of STAT3 signaling in other acute and chronic intestinal inflammatory conditions suggests that, rather than a specific feature of IBD, it represents a fundamental signaling pathway that is shared by multiple forms of gut inflammation.
authors.affiliation: Division of Gastroenterology, Ospedale San Giovanni Battista, University of Torino, Torino, Italy. mussoale@yahoo.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Musso
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dentelli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carlino
authors.forename: Luigi
authors.initials: L
authors.lastname: Chiusa
authors.forename: Alessandro
authors.initials: A
authors.lastname: Repici
authors.forename: Andreas
authors.initials: A
authors.lastname: Sturm
authors.forename: Claudio
authors.initials: C
authors.lastname: Fiocchi
authors.forename: Mario
authors.initials: M
authors.lastname: Rizzetto
authors.forename: Luigi
authors.initials: L
authors.lastname: Pegoraro
authors.forename: Carla
authors.initials: C
authors.lastname: Sategna-Guidetti
authors.forename: Maria Felice
authors.initials: MF
authors.lastname: Brizzi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003424:Crohn Disease / Q000503:physiopathology*; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000503:physiopathology*; D007413:Intestinal Mucosa; D008264:Macrophages; D008297:Male; D008875:Middle Aged; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013601:T-Lymphocytes; D015534:Trans-Activators; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators