Dipeptidyl peptidase IV activity and/or structure homologs: Contributing factors in the pathogenesis of rheumatoid arthritis?
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* Corresponding authors: Aleksi Sedo Aleksi@mbox.cesnet.cz - Jonathan S Duke-Cohan jonathan_Duke-Cohan@dfci.harvard.edu
1 Laboratory of Cancer Cell Biology of the 1st Faculty of Medicine, Charles University, Prague and the Institute of Physiology, Academy of Sciences, Prague, Czech Republic
2 Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, USA
3 Institute of Rheumatology, Prague, Czech Republic
Arthritis Research & Therapy 2005, 7:253-269 doi:10.1186/ar1852
Published: 26 October 2005Abstract
Several of the proinflammatory peptides involved in rheumatoid arthritis pathogenesis, including peptides induced downstream of tumor necrosis factor-α as well as the monocyte/T cell-attracting chemokines RANTES and stromal cell-derived factor (SDF)-1α and the neuropeptides vasoactive intestinal peptide (VIP) and substance P, have their biological half-lives controlled by dipeptidyl peptidase IV (DPPIV). Proteolysis by DPPIV regulates not only the half-life but also receptor preference and downstream signaling. In this article, we examine the role of DPPIV homologs, including CD26, the canonical DPPIV, and their substrates in the pathogenesis of rheumatoid arthritis. The differing specific activities of the DPPIV family members and their differential inhibitor response provide new insights into therapeutic design.