Activation of
signal transducer and activator of transcription 1 (STAT1) is a hallmark of IFN-gamma receptor signal transduction but is also part of the signalling pathway of other
cytokines/
growth factor receptors. In
ulcerative colitis, high levels of activation and expression of STAT1 have been observed in comparison with both
Crohn's Disease and normal controls.
Pouchitis develops in some patients after
Ileal-Pouch-Anal-Anastomosis (IPAA). The pathophysiology and aetiology of
pouchitis is still unclear. Recent studies have shown an increased production of proinflammatory
cytokines including IFN-gamma. To investigate the expression and activation of STAT1 in
pouchitis and the influence of treatment, patients were followed longitudinally from pouch operation. Diagnosis of
pouchitis was made by clinical, endoscopic and histological criteria. Biopsies were obtained during routine endoscopy and snap frozen in liquid
nitrogen. Nuclear and cytosolic extracts were prepared and the expression and activation of specific
transcription factors were assessed by Western blot, electrophoretic mobility shift assay and immunofluorescence. Patients who develop
pouchitis show highly increased levels of
STAT1 alpha as well as STAT1 beta expression and activation in comparison with both normal pouch and normal ileal mucosa. Improvement of
pouchitis during
antibiotic therapy relates to a normalization of STAT1 expression and activation. We conclude that activation of STAT1 correlates to clinical disease activity and therefore STAT1 could play an important role in the pathophysiology of
pouchitis. Similarities in the pattern of activation of STAT1 in
pouchitis and
ulcerative colitis may suggest a common pathway in the immunopathophysiology of both diseases.