Differential expression of pro-inflammatory cytokines and a pro-apoptotic protein in pelvic ileal pouches for ulcerative colitis and familial adenomatous polyposis.
BACKGROUND
Pouchitis after total rectocolectomy is among the most common complications of patients with ulcerative colitis (UC). However, its frequency is quite rare in patients with familial adenomatous polyposis (FAP). We evaluated the inflammatory and pro-apoptotic activity in endoscopically normal mucosa of the ileal pouch in patients with UC and FAP.


METHODS
Twenty patients (10 with UC and 10 with FAP) with "J" pouch after total proctocolectomy were studied as were 10 normal controls. Biopsies were obtained from the mucosa of the pouch of UC and FAP patients and from the normal ileum of controls. The expression levels of TNF-alpha, IL-1beta, IL-6, IL-8 and phospho-BAD were determined by immunoblotting. Activated NFkappaB was evaluated by immuno-precipitation and immunoblotting for IkappaB kinase beta.


RESULTS
Patients with UC had higher levels of IL-1beta, IL-6, IL-8 and TNF-alpha than patients with FAP. The level of TNF-alpha was higher in patients with UC than in patients with FAP; both patient groups had TNF-alpha levels higher than controls. Activation of NFkappaB was similar in all three groups. The expression of phospho-BAD was significantly lower in patients with FAP than in patients with UC.


CONCLUSIONS
As compared with patients with FAP, patients with UC presented increased levels of some pro-inflammatory cytokines, even in the absence of clinical or endoscopic signs of pouchitis. Patients with FAP presented lower levels of pro-inflammatory proteins and of phospho-BAD. These findings may explain the higher rates of progression to pouchitis in UC patients, which could correlate with mucosal atrophy that occurs in inflamed tissue.
Leal
R F
RF
Department of Internal Medicine Cellular Signalization Laboratory, Universidade Estadual de Campinas UNICAMP, Campinas, São Paulo, Brazil.
Coy
C S R
CS
Ayrizono
M L S
ML
Fagundes
J J
JJ
Milanski
M
M
Saad
M J
MJ
Velloso
L A
LA
Góes
J R N
JR
D011125:Adenomatous Polyposis Coli / Q000601:surgery*; D000328:Adult; D000704:Analysis of Variance; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000601:surgery*; D039021:Colonic Pouches; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D019449:Pouchitis / Q000378:metabolism*; D016737:Proctocolectomy, Restorative; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C494819:BAD protein, human; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D051025:bcl-Associated Death Protein