Protein C Signaling Impacts Inflammatory Bowel Disease

Main Category: GastroIntestinal / Gastroenterology
Also Included In: Crohn's
Article Date: 12 Jun 2007 - 20:00 PDT

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Inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis, involves both immune and nonimmune cells. Previous studies have established that the vasculature of the gut mucosa is an important nonimmune component of intestinal inflammation and that the protein C (PC) signaling pathway is an important checkpoint in the inflammatory process. Endothelial protein C receptor (EPCR) and thrombomodulin (TM) are expressed at high levels in the resting microvasculature and they convert PC into its active, anti-inflammatory form. In a study appearing online in advance of publication in the July print issue of the Journal of Clinical Investigation, Silvia Danese and colleagues from Istituto di Ricovero e Cura a Carattere Scientifico in Rozzano, Italy, show that in Crohn's disease and ulcerative colitis there is a loss of EPCR and TM expression by endothelial cells that line the intestine, which results in impaired PC activation by the inflamed mucosal microvasculature. The authors went on to show that administration of recombinant, activated PC to human intestinal endothelial cells had a potent anti-inflammatory effect and reversed experimental colitis. The results of the study suggest that that PC pathway is crucially involved in regulating intestinal inflammation triggered by changes in the mucosal microvasculature. Restoring the PC pathway may therefore represent a potential therapeutic approach to suppressing intestinal inflammation in inflammatory bowel disease.

TITLE: Crucial role of the protein C pathway in governing microvascular inflammation in inflammatory bowel disease

AUTHOR CONTACT:
Silvio Danese
Istituto di Ricovero e Cura a Carattere Scientifico, Rozzano, Italy.

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Article adapted by Medical News Today from original press release.
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JCI table of contents: June 7, 2007

Contact: Brooke Grindlinger
Journal of Clinical Investigation