Levels of dipeptidyl peptidase IV/CD26 substrates neuropeptide Y and vasoactive intestinal peptide in rheumatoid arthritis patients

Abstract

Neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) have their biological half-lives controlled by dipeptidyl peptidase IV (DPP IV/CD26). Several lines of evidence suggest the involvement of NPY in the regulation of rheumatoid arthritis (RA), and VIP has already been identified as a potent anti-inflammatory factor that reduces joint inflammation. The role of DPP IV/CD26 in the pathogenesis of RA has been indicated, but its mediator actions involving NPY and VIP have not been well investigated, so the aim of this study was to find an association between NPY, VIP, and DPP IV/CD26 in RA patients. Assessment of NPY, VIP, DPP IV/CD26 as well as some other inflammatory markers was carried out in 20 RA patients being treated with different types of drugs. Control group consisted of 18 osteoarthritis patients. Synovial fluid and serum content of investigated molecules was determined by ELISA and DPP IV/CD26 activity was measured spectrophotometrically. Immunodetection showed elevated levels of NPY and VIP in RA patients, with a significant increase in synovial fluid, while concentration and activity of DPP IV/CD26 were significantly decreased in both synovial fluid and serum. Positive correlations between serum DPP IV/CD26 concentration and activity (R = 0.6961), as well as between serum and synovial fluid concentration of VIP (R = 0.7029) were found. In RA group, NPY, VIP, and DPP IV/CD26 concentrations were not affected by the administration of drugs. The results of this study indicate a connection between elevated concentration of NPY and VIP and decreased DPP IV/CD26 activity and concentration, suggesting a potential role of these molecules in the immunomodulation of RA.

Role of vasoactive intestinal peptide in osteoarthritis

“…It was initially reported to be expressed in lung and small intestine tissue; however, currently it is also described in neurons of central nervous system (CNS) [3, 4]. Beside the neuronal source, VIP is also expressed and released from endocrine organs (such as heart, thyroid, kidney and gastrointestinal tracts) and immune organs (such as spleen, thymus, bone marrow and lymph nodes) [5].…”

“…VIP plays essential roles in a broad spectrum of biological functions. It stimulates contractility in the heart, causes vasodilation, promotes neuroendocrine-immune communication, increases glycogenolysis and lowers arterial blood pressure [1, 3]. VIP displays potent anti-inflammatory and immune-modulatory activity and modulation of VIP level has considered being a potential candidate for treatment of inflammatory and autoimmune diseases including acute pancreatitis, septic shock, inflammatory bowel disease, lipopolysaccharide (LPS)-induced acute inflammation and arthritis [6, 7].…”

Activity and expression of dipeptidyl peptidase IV on peripheral blood mononuclear cells in patients with early steroid and disease modifying antirheumatic drugs naïve rheumatoid arthritis

“…These qualitative or quantitative changes may be important in the pathogenesis of RA, since DPPIV as a result of its N-terminal X-Pro cleaving activity regulates chemotactic responses to the inflammatory chemokines CCL3- 5,11 and 22,CXCL2,[9][10][11][12], including SDF-1 [24,25]. In addition, it regulates other biologically active peptides such as NPY and VIP, recently implicated in RA [26].…”

Role of the Neutrophil Chemorepellent Soluble Dipeptidyl Peptidase IV in Decreasing Inflammation in a Murine Model of Arthritis

“…DPPIV acts on a variety of molecules that regulate leukocyte migration and activation . Whether the reduced accumulation of neutrophils and macrophages in the DPPIV‐treated mice indicates the direct effect of DPPIV in its role as a chemorepellent , and/or its role in cleaving chemoattractants, the outcome is a reduced inflammatory cell number and less tissue damage.…”