A variety of substrates that include extracellular matrix proteins, growth factors, and cytokines [23], [24], [25], [26], [27], [28] are cleaved by meprins www.selleckchem.com/products/Sunitinib-Malate-(Sutent).html whose biological function however is still poorly understood. The location and the proteolytic activity of meprins are evidence of functions at the interface of the host and the luminal environment. Meprin �� knock-out mice were more susceptible to DSS-induced experimental colitis and underwent greater colon damage and inflammation than wild-type mice [17], [29]. Meprins may act as a mucosal defence mechanism that protects the intestinal epithelium against potential toxic peptides and also against enteric commensal and pathogenic bacteria by modulating the interaction between microbes and the host mucosa.

The aims of the present study were to investigate meprin mRNA expression in ileal biopsies of CD patients since AIEC bacteria show a tropism for ileal colonization in CD patients and to analyse the role of meprins in the interaction of CD-associated E. coli and intestinal epithelial cells. Results Intestinal expression of meprins �� and �� Meprin expression was analysed by quantitative RT-PCR. The level of meprin �� mRNA expression was not significantly lower in the ileal biopsies of UC or CD patients than that of healthy controls (Fig. 1A). In contrast the level of meprin �� mRNA expression was significantly reduced in ileal biopsies of CD patients, compared to that of healthy controls (Fig. 1B, P=0.0067 Mann-Whitney U test).

Interestingly, this was independent of macroscopic inflammation, as uninvolved ileal CD biopsies alone also showed significantly less meprin �� mRNA expression than did controls (Fig. 1B, P=0.0387 after Bonferroni correction for multiple testing). Ileal biopsies from UC patients showed equally high meprin �� mRNA expression as healthy controls. Of note, among non-IBD controls two patients had diverticulitis and presented expression levels for meprin �� (1.6 and 2.4) and �� (2.7 and 3.9) close to the median, and one patient had pouchitis but the pouchitis-derived biopsy showed a rather low level for meprin �� (0.8) and almost average meprin �� expression (2.2). Figure 1 Intestinal meprin �� and meprin �� mRNA. Meprin expression was also analyzed in an adherent-invasive Entinostat E. coli (AIEC)-induced colitis model in C57BL/6J mice. We observed that both meprin �� and �� were highly expressed at the mRNA level in the ileum compared to the colon (Fig. 1C and D). No significant modified expression of both meprins was observed following AIEC reference strain LF82 infection.