No abstract

TRPA1 channels are non-selective cation channels activated by plant derived pungent products including allyl isothiocyanate (AITC) from mustard. Therefore, possible intestinal secretory functions of these channels were investigated. We detected TRPA1 mRNA in mouse and human duodenal mucosa and in intestinal mouse neuroendocrine STC-1 cells. Stimulation of STC-1 cells with AITC increased intracellular calcium ([Ca 2+ ] i ) and significantly stimulated cholecystokinin secretion by 6.7-fold. AITC induced cholecystokinin release was completely blocked by TRPA1 antagonist ruthenium red and depletion of extracellular calcium and reduced by 36% by nimodipine and nifedipine. This suggests that spices in our daily food might stimulate digestive functions.

Background: Candida albicans resides on epithelial surfaces as part of the physiological microflora. However, under certain conditions it may cause life-threatening infections like Candida sepsis. Human β-defensins (hBDs) are critical components of host defense at mucosal surfaces and we have recently shown that hBD-2 and hBD-3 are upregulated in Candida esophagitis. We therefore studied the role of Candidate signalling pathways in order to understand the mechanisms involved in regulation of hBD-expression by C. albicans. We used the esophageal cell line OE21 and analysed the role of paracrine signals from polymorphonuclear leukocytes (PMN) in an in vitro model of esophageal candidiasis.

Background: Hepatocyte growth factor (HGF) stimulates proliferation, migration and morphogenesis of epithelial cells by specific binding to its receptor c-met. Overexpression of HGF or c-met has been reported for human gastric or pancreatic cancer. In colorectal cancer overexpression of c-met but not HGF has been shown. However, elevated HGF serum levels have been detected in colorectal cancer patients. Therefore, the present study was performed to investigate expression patterns of both c-met and HGF in colorectal cancers and metastasis in comparison to normal mucosa. Furthermore, the mitogenic actions of HGF on colorectal cancer cells were studied in vitro. Methods: Expression of c-met and HGF were analyzed by RT-PCR and Western blotting and localized in the tissues utilizing immunohistochemistry. Mitogenic effects of HGF were determined in four human colon cancer cell lines by ³H-thymidine incorporation studies. Results: C-met and HGF mRNA were detectable in 60% of the normal specimen, but in the majority of cancer samples, and in just 33% of the liver metastasis. In cancer samples a coexpression of c-met and HGF was detected in 77% of the specimens. The extent of protein expression of receptor and ligand correlated with the mRNA expression. Moreover, c-met protein expression was increased 2- to 3-fold in colorectal cancers. C-met was detected in cells of epithelial origin, whereas HGF was expressed by mesenchymal cells. In vitro, HGF significantly stimulated cell growth in all four cell lines. Conclusion: Overexpression of c-met protein in colorectal cancers is combined with an expression of HGF in the majority of cases suggesting a paracrine manner of growth enhancement, while only a weak expression of c-met or HGF was detected in metastatic tissues.

No abstract

Development of pouchitis correlates with decreased defensin expression in ulcerative colitis in addition to high expression of cytokines. The low incidence of pouchitis in FAP pouches correlates with increased expression of hBD-1 beta-defensin in association with low cytokine levels.

The intestinal mucosa has to withstand exposure to a variety of substances, challenges in pH, temperature, and osmolarity; and, finally, bacterial products which might induce local and systemic inflammatory responses. The mucosal integrity is conserved by a defense system which consisting of constitutive and inducible mechanisms. These include the physical barrier function; the secretion of factors into the lumen, such as mucins and antibacterial substances; the mucosal immune system; and, finally, the ability of the mucosa to reconstitute once damage has occurred. The homeostasis and integrity of the gastrointestinal mucosa ultimately depends upon the balance between defensive and aggressive factors. While the physical barrier function was formerly believed to play the major role in mucosal protection against luminal bacteria, the recent discovery of Toll-like receptors and antimicrobial peptides in the intestinal epithelium has modified the concept of intestinal defense towards a more active character, which will be discussed in this review.

The measurement of stool PK could be a potentially useful marker of IBD activity in children. However, its clinical value demands further studies for comparison with other tests.