Activation of signal-transducer and activator of transcription 1 (STAT1) in pouchitis

Activation of signal transducer and activator of transcription 1 (STAT1) is a hallmark of IFN-gamma receptor signal transduction but is also part of t he signalling pathway of other cytokines/growth factor receptors. In ulcera tive colitis, high levels of activation and expression of STAT1 have been o bserved in comparison with both Crohn's Disease and normal controls. Pouchi tis develops in some patients after Ileal-Pouch-Anal-Anastomosis (IPAA). Th e pathophysiology and aetiology of pouchitis is still unclear. Recent studi es have shown an increased production of proinflammatory cytokines includin g IFN-gamma. To investigate the expression and activation of STAT1 in pouch itis and the influence of treatment, patients were followed longitudinally from pouch operation. Diagnosis of pouchitis was made by clinical, endoscop ic and histological criteria. Biopsies were obtained during routine endosco py and snap frozen in liquid nitrogen. Nuclear and cytosolic extracts were prepared and the expression and activation of specific transcription factor s were assessed by Western blot, electrophoretic mobility shift assay and i mmunofluorescence. Patients who develop pouchitis show highly increased lev els of STAT1 alpha as well as STAT1 beta expression and activation in compa rison with both normal pouch and normal ileal mucosa. Improvement of pouchi tis during antibiotic therapy relates to a normalization of STAT1 expressio n and activation. We conclude that activation of STAT1 correlates to clinic al 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.