Signal transducers and activators of transcription 3 signaling pathway. An Essential Mediator of Inflammatory Bowel Disease and Other Forms of Intestinal Inflammation

• Published in: Inflammatory bowel diseases 2005-02, Vol.11 (2), p.91-98
• Main Authors: Musso, Alessandro, Dentelli, Patrizia, Carlino, Alessandra, Chiusa, Luigi, Repici, Alessandro, Sturm, Andreas, Fiocchi, Claudio, Rizzetto, Mario, Pegoraro, Luigi, Sategna‐Guidetti, Carla, Brizzi, Maria Felice
• Format: Article
• Language: English
• Subjects: Adult; Biopsy; Case-Control Studies; Celiac disease; Cell activation; Crohn Disease - physiopathology; Crohn's disease; Cytokines; Digestive tract; DNA-Binding Proteins; Female; Humans; Immunoblotting; Immunofluorescence; Inflammation; inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - physiopathology; intestinal inflammation; Intestinal Mucosa; Intestine; lamina propria; Leukocytes (mononuclear); Leukocytes (neutrophilic); Lymphocytes T; Macrophages; Male; Middle Aged; Mucosa; Mucosal immunity; Peripheral blood mononuclear cells; Signal Transduction; STAT3; Stat3 protein; STAT3 Transcription Factor; T-Lymphocytes; Trans-Activators; Transcription; Transcriptional Activation; Ulcerative colitis
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1097/00054725-200502000-00001

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.