ADAM15 up‐regulation in inflammatory bowel disease and cooperation with multiple partners

A Disintegrin And Metalloprotease (ADAM)15 is characterized by adhesive function through its RGD domain interaction with some integrin subunits, and protease properties. The goal of this work was to describe the tissue distribution of ADAM15 and its spatial relationship with its known binding partners in inflammatory bowel disease (IBD). In the normal colon, ADAM15 was expressed at the baso‐lateral membrane of all epithelial cells throughout the crypt, as well as by endothelial cells. In IBD, ADAM15 was strongly upregulated at the mRNA level and expressed only as an active form as shown by immunoblotting. Parallel to its upregulation, ADAM15 was expressed both at the plasma membrane and in the cytoplasm of epithelial cells in acute attacks of the disease. In the crypt abcesses, ADAM15‐positive epithelial cells were in close contact with integrin‐positive inflammatory cells. In the inflammatory infiltrate and ulcerative areas, α4β1 integrin‐positive mononuclear cells established close contact with ADAM15‐positive vessels. In the regenerative areas, ADAM15 positive epithelial cells were in close contact with α5β1‐positive pericryptic myofibroblasts. In conclusion, there is a differential expression of ADAM15 in epithelial cells during IBD compared with the normal colon. This study suggests a role for ADAM15 in the differentiation of regenerative colonic mucosa and in leukocyte transmigration across epithelial and endothelial barriers. Granted by French Ministère de la Recherche (ACIM A03038 GS) and by NIH ( DK061941 ‐02).