Inflammatory and apoptosis pathway in ileal pouches of patients with ulcerative colitis and familial adenomatous polyposis / Estudo da atividade inflamatoria e apoptose em reservatorios ileais de doentes operados por polipose adenomatosa familiar e retocolite ulcerativa inespecifica

AUTOR(ES)

Raquel Franco Leal

DATA DE PUBLICAÇÃO

2009

RESUMO

Ileal pouch-anal anastomosis is the surgical procedure of choice for patients with refractory ulcerative colitis (UC) and for familial adenomatous polyposis (FAP) with rectal polyps. Pouchitis is the most common complication in UC, while it is quite rare in FAP. Objective: Evaluate the inflammatory and apoptotic activity in endoscopically normal ileal pouch mucosa, by determining the expressions of IFN-?, STAT-1, IL-10, SOCS-3, Bax, Bcl-2, FADD/Caspase-8 and Apaf-1/Caspase-9 in operated patients with UC and FAP. Patients and Methods: Eighteen patients submitted to total retocolectomy and J pouch were evaluated; nine were patients with UC and nine with FAP. The control group consisted of nine individuals with normal ileo-colonoscopy examination. The collected specimens were snap-frozen in liquid nitrogen and expressions of IFN-?, STAT-1, IL-10, SOCS-3, Bax and Bcl-2 were determined by immunoblot of total protein extracts. FADD/Caspase-8 and Apaf-1/Caspase-9 were evaluated by immunoprecipitation and immunoblot. Immunohistochemistry analysis for Bax and Bcl-2, and immunofluorescence with Annexin V assays were applied in all biopsies. Results: STAT-1 expression was increased in patients with UC, when compared with FAP and controls (p<0.05). IFN-? expression was increased in UC when compared with controls (p<0.05). IL-10, SOCS-3 and Bcl-2 were similar among the groups (p>0.05). Apaf-1/Caspase-9 expression was increased in UC when compared with FAP (p<0.05); however FADD/Caspase-8 was similar in the groups (p>0.05). Conclusion: Patients with UC had increased pro-inflammatory cytokines levels, even without clinical and endoscopic evidence of pouchitis; these alterations were similar to those of UC disease. Indeed, there was increased pro-apoptotic protein expression in UC. These findings may suggest a higher susceptibility to this complication in operated patients with UC, when it was compared to PAF. In addition, a down-regulation of apoptosis in FAP was observed, possibly explaining the decreased cell turn over and presence of adenomas in this syndrome

ASSUNTO(S)

intestino - doenças molecular biology cirurgia surgery biologia molecular intestinal disease

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