Previous molecular dissections of virulence factor expression in the AIEC protein inhibitors reference strain LF82 suggested that these bacteria are highly piliated under physiological conditions in the gastrointestinal tract [16]. Any proteolytic degradation of type 1 pili could modify the behaviour of the AIEC bacteria within the host, and any decrease in protease expression could therefore increase AIEC colonization of the ileal mucosa. AIEC infection of IECs induces the secretion of high amounts of the pro-inflammatory cytokine IL-8, a potent chemoattractant for neutrophils [7]. We observed that when AIEC LF82 bacteria were treated by meprin �� or ��, IL-8 secretion by infected IECs was significantly decreased. This effect was probably due to the decrease in the ability of bacteria to adhere to and invade intestinal epithelial cells as a consequence of proteolytic degradation of type 1 pili.

These results are in accordance with our previous study showing that the inflammation induced by AIEC infection of mice expressing the human CEACAM6 was not observed when the AIEC LF82 type 1 pili�Cnegative mutant was used [13]. It can be speculated that down-regulation of meprin expression observed in CD patients leading to impaired meprin secretion/retention at the epithelial brush border might favor not only colonization of the intestinal mucosa by AIEC bacteria but also AIEC-induced inflammation of the gut. Materials and Methods Patients and controls CD: n=27, mean age 41 years (25-88), 12 male and 15 female patients. UC: n=6, mean age 45 years (21�C65), 2 male and 4 female patients.

Controls: n=18, mean age 55 years (38�C74), 9 male and 9 female non-IBD individuals/patients. Biopsies were collected during routine (patients) or screening (controls) endoscopic examination at the Gastroenterology unit, University Hospital Bern, Bern, Switzerland. Biopsies were chosen solely upon their location and macroscopic appearance, as judged by the experienced endoscopist. CDAI and Mayo scores, although determined routinely, were not used to stratify the cohort of patients used in the present study. Informed written consent to use biopsies for the present study was obtained from all patients, and all procedures were approved by the ethical committee of the local authorities of the Canton of Bern. Mouse model and infection Nine-week-old C57BL/6J (B6) mice (��19.

5 g) were bred and reared at the central animal facility of the medical faculty of the University of Bern, Switzerland. They received DSS (MW=36,000�C50,000, MP Biomedicals, Illkirch, France) in drinking water for 7 days with 3.5% (w/v) DSS for the first 3 days and 2.5% (w/v) DSS for the last 4 days. The mice were orally challenged by 5 mg of streptomycin Anacetrapib (Sigma) at day 3 and by 108 AIEC LF82 bacteria at day 4. They were sacrified at day 7 and the ileum and colon were collected.