Dipeptidyl peptidase IV activity and/or structure homologs: Contributing factors in the pathogenesis of rheumatoid arthritis?

Aleksi Sedo¹ , Jonathan S Duke-Cohan² , Eva Balaziova¹ and Liliana R Sedova³

¹Laboratory of Cancer Cell Biology of the 1^stFaculty of Medicine, Charles University, Prague and the Institute of Physiology, Academy of Sciences, Prague, Czech Republic

²Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, USA

³Institute of Rheumatology, Prague, Czech Republic

author email corresponding author email

Arthritis Research & Therapy 2005, 7:253-269doi:10.1186/ar1852


Published:	26 October 2005

Abstract

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.