interleukin-8 and Adenomatous-Polyposis-Coli

Accumulated evidences supported IL-8 play an important role during colorectal carcinogenesis. However, few direct-related evidences are available. In this paper, we found that high level of IL-8 was constitutively present both in familial adenomatous polyposis (FAP) tissue and carcinoma tissue. Using primary epithelial cells from FAP samples, we study IL-8 effect on their growth, migration, and colonies formation. The results showed that IL-8 stimulated cells proliferation, migration, and colonies formation. Furthermore, High level of CEA, CK20, and EGFR was detected after exposure to IL-8 in primary epithelial cells. In conclusion, our findings showed that IL-8 promotes the adenoma-carcinoma transition in primary epithelial cells from FAP. Targeting IL-8 at adenoma stage may prevent or reduce carcinogenesis.

Topics: Adenomatous Polyposis Coli; Carcinoembryonic Antigen; Carcinogenesis; Cell Movement; Cell Proliferation; Epithelial Cells; ErbB Receptors; Humans; Interleukin-8; Keratin-20; RNA, Messenger; Tumor Cells, Cultured

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.. 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.. 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.. 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.

Topics: Adenomatous Polyposis Coli; Adult; Analysis of Variance; Apoptosis Regulatory Proteins; bcl-Associated Death Protein; Colitis, Ulcerative; Colonic Pouches; Cytokines; Female; Humans; Immunoblotting; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; NF-kappa B; Pouchitis; Proctocolectomy, Restorative; Tumor Necrosis Factor-alpha