Journal
FASEB JOURNAL
Volume 22, Issue 3, Pages 641-653Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.07-8876rev
Keywords
metargidin (MDC-15); cell-cell interactions; cell-matrix interactions; inflammatory diseases; proteases
Categories
Funding
- NIDDK NIH HHS [R24-DK-064399, R01-DK-071594, R01-DK-061941] Funding Source: Medline
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R24DK064399, R01DK071594, R01DK061941] Funding Source: NIH RePORTER
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Cell-cell and cell-matrix interactions are of utmost importance in the pathogenesis of inflammatory diseases. For example, cell-cell and cell-matrix interactions are crucial for leukocyte homing and recruitment to inflammatory sites. The discovery of the disintegrin and metalloprotease (ADAM) proteins, which have both adhesive and proteolytic activities, raised the question of their involvement in inflammatory processes. More interestingly, the presence of the RGD integrin-binding sequence in the disintegrin domain of ADAM-15 (MDG15; metargidin) highlighted ADAM-15 as a protein particularly involved in cell-cell interactions. These findings therefore prompted authors to investigate the roles of ADAM-15 in inflammatory diseases. Because of the early description of ADAM-15 expression in endothelial cells, work first focused on the roles of ADAM-15 in vascular diseases, and ADAM-15 was found to be associated with atherosclerosis. Other studies also pointed at ADAM-15 as a mediator of rheumatoid arthritis and intestinal inflammation as well as inherent angiogenesis. The roles of ADAM-15 in these diseases appear to involve mechanisms as different as cell-cell interactions, cell-extracellular matrix (ECM) interactions, and shedding activity. Here we review and discuss these recent discoveries pointing to ADAM-15 as a mediator of mechanisms underlying inflammation and as a possible therapeutic target for prevention of inflammatory diseases.
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