Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009319 (colitis)
 19,384 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The association of hepatobiliary disorders with colonic inflammation is well recognized. Although the pathophysiology is obscure, increased permeation of toxic bacterial products across the inflamed gut to the portal circulation might be one mechanism. Potentially toxic metabolites include N-formylated chemotactic peptides that are produced by several species of intestinal bacteria and can be detected in colonic fluid in vivo. To investigate the metabolic fate of one of these low molecular weight proinflammatory peptides, N-formyl L-methionine L-leucine 125I-L-tyrosine was introduced into colon loops of healthy rats (n = 10) and rats with experimental colitis (n = 15) induced by rectal instillation of 15% (vol/vol) acetic acid. Gut, liver, and blood radioactivity were monitored by external gamma-counting and radioactivity in bile was measured by biliary catheter drainage into a well counter. Bile was processed by high-performance liquid chromatography to determine the amount of intact, bioactive peptide excreted over 3 h. After colonic instillation of 1 nmol of peptide, the mean (+/- SEM) biliary excretion of intact peptide was 6.4 +/- 2.0 pmol in normal rats and 49.0 +/- 20 pmol in rats with colitis (p less than 0.01). An enterohepatic circulation of synthetic N-formyl L-methionine L-leucine L-tyrosine has been demonstrated in the rat. Experimental colitis was associated with an eightfold increase in biliary excretion of this proinflammatory bacterial peptide. Proinflammatory bacterial peptides synthesized by colonic bacteria could be important in the pathophysiology of colon inflammation and its frequently associated hepatobiliary complications.
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PMID:Enterohepatic circulation of bacterial chemotactic peptide in rats with experimental colitis. 334 70

Primary sclerosing cholangitis (PSC) frequently accompanies inflammatory bowel diseases. In an attempt to increase our understanding of the pathogenesis of PSC, we studied bile duct changes in rats with colitis which had been given N-formyl L-methionine L-leucine L-tyrosine (fMLT) rectally; fMLT is one of the chemotactic peptides produced by Escherichia coli, and is secreted into the bile by hepatocytes after it enters the portal blood. Transrectal administration of fMLT induced a marked inflammation in the portal triad and mild hepatocyte necrosis on the 4th day. The infiltrating leukocytes in the portal tract were mostly mononuclear cells, which densely infiltrated around the bile ducts. These mononuclear cells appeared to attach to bile duct epithelial cells, and they were more numerous in the smaller bile ducts. Electron microscopy revealed that lymphocytes were in direct contact with bile duct lining cells and that some epithelial cells had degenerated or collapsed. These results suggest that this E. coli-derived peptide may induce cholangitis in the small bile duct through cell-mediated mechanisms. Since these pathologic changes resemble those of the bile duct observed in the early stage of PSC, it can be concluded that bacterial chemotactic peptides may play a role in the pathogenesis of small-duct PSC.
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PMID:Small duct cholangitis induced by N-formyl L-methionine L-leucine L-tyrosine in rats. 800 May 12