rn-1734 and Inflammatory-Bowel-Diseases

The transient receptor potential vanilloid-4 (TRPV4) belongs to a family of ion channels and can be activated by warm temperature, hypotonicity, cell swelling or lipid mediators of the arachidonic cascade. The metabolites or events responsible for TRPV4 activation are associated with inflammation, arguing in favor of a role for this receptor in inflammatory diseases. The first studies have focused their attention on the role of TRPV4 in neurons and endothelial cells but TRPV4 cellular distribution is widespread, particularly in the gastrointestinal tract. Herein, we review a number of studies demonstrating the expression of TRPV4 in the gut, the regulation of its expression and functions by inflammatory mediators in that organ and the consequences of TRPV4 activation or inhibition in the intestine. We further discuss the relevance of considering this receptor as a potential target for therapeutic development in inflammatory bowel diseases.

Topics: Animals; Drug Delivery Systems; Humans; Inflammation Mediators; Inflammatory Bowel Diseases; Intestinal Mucosa; Pain; Sulfonamides; TRPV Cation Channels

Recent reports suggested that the activation of Transient Receptor Potential Vanilloid 4 (TRPV4) receptors in the gastrointestinal tract has pro-inflammatory effects. In this study, we demonstrated for the first time that TRPV4 mRNA expression is up-regulated in patients with inflammatory bowel diseases (IBD). Furthermore, selective blockade of TRPV4 in the 2,4,6-trinitrobenzenesulfonic acid animal model alleviates colitis and pain associated with the intestinal inflammation. Our study indicates that TRPV4 may play a role in mechanisms of defense in intestinal inflammation and that TRPV4 may be an attractive target for future systemic or topic anti-inflammatory treatment in patients with IBD.

Topics: Animals; Disease Models, Animal; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Mice; Pain; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Sulfonamides; TRPV Cation Channels