Activities of dipeptidyl peptidase II and dipeptidyl peptidase IV in mice with lupus erythematosus-like syndrome and in patients with lupus erythematosus and rheumatoid arthritis.

Hagihara, Mao; Ohhashi, M; Nagatsu, T

doi:10.1093/clinchem/33.8.1463

Cited by 34 publications

(19 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Shedding of DPP4 from different tissues seems to be varied at different disease conditions. For example, plasma DPP4 levels are increased in T2DM, obesity, NAFLD, cancer, renal graft rejection , osteoporosis where as it is decreased in rheumatoid arthritis (RA; ) and pregnancy .…”

Section: Sources Of Circulatory Dpp4 In Metabolic Diseasesmentioning

confidence: 99%

Significance of circulatory DPP4 activity in metabolic diseases

Nargis

Chakrabarti

2018

IUBMB Life

View full text Add to dashboard Cite

Dipeptidyl peptidase 4 (DPP4), also known as CD26 is a type II transmembrane protein that is released from the cell membrane in a nonclassical secretory mechanism. This exopeptidase selectively degrades varieties of substrates including incretin hormones, growth factors, and cytokines. A significant detectable amount of DPP4 activity can be measured in plasma as well as in different tissues such as intestinal epithelium, vascular endothelium, lymphocytes, monocytes, kidney, liver, adipose, lung, thymus, spleen, prostate, etc. Enzymatically active circulatory DPP4 is shed from the plasma membrane via proteolytic cleavage, a process responsible for the enhanced plasma DPP4 levels and activity. Elevated circulatory DPP4 activity as well as levels has been found in wide spectrum of metabolic diseases including diabetes, obesity, cardiovascular diseases, and nonalcoholic fatty liver diseases. Moreover, recent preclinical studies have further expanded the repertoire for the usage of DPP4 inhibitors in the treatment of other metabolic diseases and in their consequent complications. In the present review we highlight the reason behind the elevated circulatory DPP4 levels in metabolic diseases with a focus on the tissue of origin. We also underscore the discrepancy of protein levels with enzyme activity of circulatory DPP4 in metabolic diseases. © 2018 IUBMB Life, 70(2):112-119, 2018.

show abstract

Section: Sources Of Circulatory Dpp4 In Metabolic Diseasesmentioning

confidence: 99%

Significance of circulatory DPP4 activity in metabolic diseases

Nargis

Chakrabarti

2018

IUBMB Life

View full text Add to dashboard Cite

show abstract

“…In RA, decreased DPPIV enzymatic activity was observed in blood plasma/sera compared with healthy controls [ 32 ]. Further studies demonstrated a significant inverse correlation of serum DPPIV activity with disease severity as determined by C-reactive protein concentration, the number of swollen joints and with the Disease Activity Score 28 [ 33 - 35 ].…”

Section: Dash Molecules In Rheumatoid Arthritismentioning

confidence: 99%

“…The relationship of DPPII/QPP/DPP7 activity to CD26-related enzyme activity is complex in that DPPII activity increases in the plasma of RA patients, while DPPIV decreases [ 32 ]. This suggests that, overall, DASH activity may be less critical than individual substrate specificity, which may be influenced in large part by initial subcellular localization rather than plasma levels.…”

Section: Dash Molecules In Rheumatoid Arthritismentioning

confidence: 99%

Untitled

et al. 2005

View full text Add to dashboard Cite

253 ADA = adenosine deaminase; CCL = CC ligand; CCR = CC receptor; CGRP = calcitonin gene-related peptide; CXCL = CXC ligand; CXCR = CXC receptor; DASH = dipeptidyl peptidase-IV activity and/or structure homologues; DPP = dipeptidyl peptidase; FAP-α = fibroblast-activation protein α/seprase; GLP-1 = glucagon-like peptide-1; GRP = gastrin releasing peptide; HLA = human leukocyte antigens; IFN = interferon; IL = interleukin; IP-10 = IFN-γ inducible protein-10; Mig = monokine induced by interferon-γ; MIP = macrophage inflammatory protein; NAALADase = N-acetylated α-linked acidic dipeptidase; NK = natural killer; NPY = neuropeptide Y; OA = osteoarthritis; PB = peripheral blood; QPP = quiescent cell proline dipeptidase; RA = rheumatiod arthritis; RANTES = regulated upon activation normal T-cell expressed and secreted; SDF = stromal cellderived factor; SF = synovial fluid; SLE = systemic lupus erythematosus; SP = substance P; TGF = transforming growth factor; TNF = tumor necrosis factor; VIP = vasoactive intestinal peptide. Available online http://arthritis-research.com/content/7/6/253 AbstractSeveral 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.

show abstract

“…In mouse models of T cell-mediated autoimmunity, inhibitors of DPP-4 can reduce disease severity and are associated with increases in transforming growth factor (TGF)-β levels and improvements in immune tolerance induction [18,19]. Interestingly, in human autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, increased CD26 levels on leucocytes are observed, yet there is decreased DPP-4-associated peptidase activity [20][21][22]. The reason for the discrepancy between activity and membrane CD26 levels is unclear, but this could be due to decreased shedding of CD26 from the membrane or decreased levels of other peptidases that cleave the same substrate.…”

Section: Introductionmentioning

confidence: 99%

Effects of short-term sitagliptin treatment on immune parameters in healthy individuals, a randomized placebo-controlled study

Price

Linder

et al. 2013

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SummarySitagliptin, a dipeptidyl-peptidase 4 (DPP-4) inhibitor, improves blood glucose control in patients with type 2 diabetes by blocking cleavage of glucagon-like peptide 1 (GLP-1). In type 2 diabetes patients sitagliptin use is associated with an increase in minor infections, and in new-onset type 1 diabetes patients the ability of sitagliptin to dampen autoimmunity is currently being tested. DPP-4, also known as CD26, is expressed on leucocytes and can inactivate many chemokines important for leucocyte migration, as well as act as a co-stimulatory molecule on T cells. Therefore, this study was conducted to test whether sitagliptin is immunomodulatory. In this randomized, placebo-controlled trial, healthy volunteers were given sitagliptin or placebo daily for 28 days, and blood was drawn for immune assays. No significant differences were observed in the percentage of leucocyte subsets within peripheral blood mononuclear cells (PBMCs), plasma chemokine/cytokine levels or cytokines released by stimulation of PBMCs with either lipopolysaccharide (LPS) or anti-CD3. Individuals taking sitagliptin displayed increases in the percentage of cells expressing higher levels of CD26 at early time-points compared to placebo controls, but these differences resolved by day 28 of treatment. Therefore, in healthy volunteers, treatment with sitagliptin daily for 28 days does not overtly alter systemic immune function.

show abstract

Activities of dipeptidyl peptidase II and dipeptidyl peptidase IV in mice with lupus erythematosus-like syndrome and in patients with lupus erythematosus and rheumatoid arthritis.

Cited by 34 publications

References 0 publications

Significance of circulatory DPP4 activity in metabolic diseases

Significance of circulatory DPP4 activity in metabolic diseases

Untitled

Effects of short-term sitagliptin treatment on immune parameters in healthy individuals, a randomized placebo-controlled study

Contact Info

Product

Resources

About