Activation of the JAK-STAT system in pouchitis

Background and Aim: Patients with ulcerative colitis, who had undergone tot al colectomy and restorative proctosurgery, develop in 10-30% an inflammati on of the ileal pouch mucosa. Immunopathogenesis of pouchitis is unclear. I t is discussed to be a third iatrogenic form of IBD or a recurrence of ulce rative colitis. An increased expression of proinflammatory cytokines can be found in ulcerative colitis and Crohn's disease. In ulcerative colitis hig h levels of activation and expression of the transcription factor STAT1 can be seen in comparison with Crohn's disease. An activation of NF kappa B ca n be found in both diseases (GUT 1998, 42:477-484). The aim of our study wa s to investigate the expression and activaton of cytokine transcription fac tors in pouchitis before and after an antibiotic treatment. Methods: Biopsies were taken during routine endoscopies and cytosolic, nucl ear and whole cell extracts were prepared. Expression and activation of STA T1, TAK1, NF kappa B and I kappa B was analyzed by Western Blot, Electropho retic Mobility Shift Assay and Immunofluorescence. Results: An increased expression and activation of STAT1 and its kinase TAK 1 can be found in the lamina propria of patients with pouchitis in comparis on to non inflamed pouch and normal ileum. Antibiotic treatment results in normalisation of STAT1 activation. NF kappa B is activated in pouchitis. Conclusions: Expression and activation of the transcription factor STAT1 an d the kinase JAK1 is increased in patients with pouchitis. Pouchitis shows similiarities in the activation and expression pattern of transcripton fact ors with ulcerative colitis but not Crohn's disease.