Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the activity of peptidases in the serum of mice with experimental polyarthritis that was induced by the injection of type II collagen, an experimental model of human rheumatoid arthritis. The activity of dipeptidyl peptidase II (DPP II) was increased and that of dipeptidyl peptidase IV (DPP IV) was decreased resulting in the significant increase of the serum DPP II/DPP IV ratio in the polyarthritic mice compared with that of controls. These results indicate that the DPP II/DPP IV ratio is a novel index of disease activity in mice with collagen-induced polyarthritis and may be useful in assessing the activity of rheumatoid arthritis in humans.
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PMID:The activity of dipeptidyl peptidase II and dipeptidyl peptidase IV in mice immunized with type II collagen. 136 72

Human skin fibroblasts were probed for cell surface protease activity. One activity removing dipeptides from the NH2-terminal end of Gly-Pro-pNA was specifically inhibited by di-isopropyl-fluorophosphate (DFP), phenylmethanesulphony fluoride (PMSF), and diprotin A, and thus was identified as dipeptidyl peptidase IV (DPP IV). A group of bestatin-sensitive N-exoaminopeptidase activities was also characterized when Ala-, Leu-, and Arg-pNA were used as chromogenic substrates. Using human monoclonal antibodies anti-CD 13 and anti-CD 26 that recognized, respectively, an N-Ala-aminopeptidase and DPP IV, it was found that human dermal fibroblasts expressed the CD 13 and CD 26 antigen on their surface. In addition, both peptidases were specifically immunoprecipitated by monoclonal antibodies anti-CD 13 and anti-CD 26 from plasma membranes. Cell surface proteolytic activities were also investigated in human fibroblasts derived from dermatological and rheumatic diseases (i.e., psoriasis, rheumatoid arthritis, and lichen planus). It was found that these fibroblasts also expressed both types of proteinases initially identified on normal skin fibroblasts and that the levels of Ala-aminopeptidase activities were similar in all cases. In contrast, the levels of Arg-, Leu-exoaminopeptidase, and DPP IV activities were significantly higher (up to 6.6-fold) in the three pathological fibroblast populations than in their normal counterparts. These proteolytic enzymes, therefore, can potentially serve as markers in dermatological diseases. Taken together, our results suggest that skin fibroblast-derived proteinases associated with both serine and N-aminopeptidase activities may play an important role by participating in the extracellular events associated with fibroblast behaviour.
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PMID:Characterization of specific proteases associated with the surface of human skin fibroblasts, and their modulation in pathology. 157 9

The activities of collagenase-like peptidase, estimated by using (succinyl-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro)-4-methylcoumaryl-7-amide as substrate, and of dipeptidyl-aminopeptidase IV were decreased in the sera from patients with rheumatoid arthritis. Both enzymes bring about the degradation of peptides derived from collagen. A significant positive correlation was observed between the activities of the two serum peptidases.
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PMID:Collagenase-like peptidase activity in serum from patients with rheumatoid arthritis. 285 19

We examined the activities of peptidases in plasma and tissues of the New Zealand Black (NZB) mouse as an animal model of human systemic lupus erythematosus, and also in serum from patients with rheumatoid arthritis and systemic lupus erythematosus. Activities of dipeptidyl peptidase II (DAP II) and post-proline cleaving enzyme (PPCE) were increased, and dipeptidyl peptidase IV (DAP IV) activity was decreased in plasma and spleen of NZB mice, as compared with the control BALB/c mice. Likewise, the activity of DAP II was increased and that of DAP IV was decreased in serum of patients with rheumatoid arthritis and systemic lupus erythematosus. These results indicate the importance of hydrolytic enzymes in the pathogenesis of autoimmune diseases.
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PMID: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. 288 36

It is known that the serum level of glycylproline aminopeptidase (Gly-Pro-AP) is decreased in the patients with rheumatoid arthritis. In the present study, the serum levels of various hydrolytic enzymes were tested in such patients. In comparison to the controls, many enzymes, including Ala-AP, Ser-AP, Phe-AP, Gly-Pro-AP, Gly-Pro-Leu-AP, dipeptidyl carboxypeptidase (angiotensin converting enzyme), and esterase, showed significantly decreased activities in the patients' sera. Only the activity of Trp-AP was significantly increased. Of these enzymatic activities in serum, several ones including those of Gly-Pro-AP, Ala-AP, Phe-AP, trypsin-like enzyme, and esterase, were significantly correlated with the severity of the disease. Although a part of these findings are compatible with previous observations, they suggest rather more extensive disorders of peptide metabolism in this immunological disease.
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PMID:Decreased serum levels of various hydrolytic enzymes in patients with rheumatoid arthritis. 608 27

Using biochemical methods glycylprolyl-diaminopeptidase (GP-DAP, EC 3.4.14.5) was measured in purified leukocyte subpopulations and found selectively in T lymphocytes. In 129 subjects with normal hepatic function a significant correlation was observed between the serum GP-DAP activity and the peripheral blood lymphocyte count. In four patients suffering from rheumatoid arthritis, four weeks of thoracic duct drainage resulted in a reduction of the peripheral blood lymphocyte count and a concomitant decrease of the serum GP-DAP activity. These observations suggest that lymphocytic GP-DAP may contribute to the total serum GP-DAP activity.
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PMID:Glycylprolyl-diaminopeptidase in human leukocytes: selective occurrence in T lymphocytes and influence on the total serum enzyme activity. 614 12

Plasminogen (Pg) activation on the surface of rheumatoid arthritis (RA) synovial fibroblasts by the urinary-type Pg activator induced a significant increase in cytosolic free Ca2+ concentration. This response was not observed in normal synovial fibroblasts, suggesting different Pg binding and activation mechanisms in these cell types. Pg receptors from both cell types were isolated by affinity chromatography using Pg covalently bound to Sepharose 4B. RA synovial fibroblasts express a Pg receptor complex composed of a glycoprotein IIb/IIIa-related protein in association with a 130-kDa protein that is antigenically related to the alpha 2-macroglobulin receptor-associated protein and dipeptidyl peptidase IV. This receptor complex appears to bind to both Pg and fibronectin. The Pg "receptor" in normal synovial fibroblasts is composed of a 97-kDa protein also antigenically related to the alpha 2-macroglobulin receptor-associated protein. Both cell types express the urinary-type Pg activator receptor on their surfaces. Our results suggest that RA synovial fibroblasts express novel proteins involved in Pg binding, activation, and signal transduction, which are absent in normal synovial fibroblasts.
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PMID:Characterization of the plasminogen receptors of normal and rheumatoid arthritis human synovial fibroblasts. 790 77

We evaluated the immunopharmacological effects of two novel dipeptidyl peptidase IV (DP IV) inhibitors, TMC-2A [(2S,2S',2S'')-2-[2'-[2''-amino-3''-(-indol-3'''-yl)-1''-oxopropyl]-1',2 ',3',4'-tetrahydro-6',8'-dihydroxy-7'-methoxyisoquinol-3-yl-car bonylamino]-4-hydroxymethyl-5-hydroxypentanoic acid] and TSL-225 (tryptophyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid). TMC-2A, produced by Aspergillus sp. A374, inhibited rat kidney DP IV uncompetitively, with a Ki value of 5.3 microM. In vivo, TMC-2A suppressed alkyldiamine (N,N-dioctadecyl-N',N-bis(2-hydroxyethyl)propanediamine)-induced arthritis. We developed a chemically modified inhibitor, TSL-225, with potency similar to that of TMC-2A. TSL-225 inhibited DP IV uncompetitively, with a Ki value of 3.6 microM. TSL-225 was also effective against adjuvant-induced arthritis. These results suggest that TMC-2A and its derivatives may have therapeutic potential for the treatment of inflammatory diseases such as rheumatoid arthritis.
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PMID:Anti-arthritic effects of the novel dipeptidyl peptidase IV inhibitors TMC-2A and TSL-225. 977 75

The extracellular domain of the T cell co-stimulatory molecule CD26 possesses dipeptidyl peptidase IV (DP IV) enzyme activity. Activated T cells are known to increase expression of cell surface DP IV and some specific inhibitors of this enzyme have been reported to suppress T cell function. Previously we have identified a DP IV inhibitor, designated TMC-2, found in culture supernatant of Aspergillus oryzae. Administration of TMC-2 to rats with adjuvant arthritis caused marked suppression of paw swelling. To elucidate the mechanism of TMC-2 antiarthritic activity, we have studied its effects on T cell function. Here we show that TMC-2 inhibited DP IV activity of CD26 immunoprecipitated from T cell lysates, and also inhibited proliferative responses of T cells to specific antigen or anti-CD3 antibody. Suppression of IL-2 production was demonstrated at both the mRNA and protein levels. TMC-2 did not alter the PTPase activity of pure CD45, but when this molecule was co-precipitated from T cell lysates together with associated CD26, its PTPase was virtually completely abolished by TMC-2. These results suggest that modulation of CD45 PTPase activity might be responsible for functional suppression of T cells by TMC-2. Because the effects of TMC-2 on T cells were reversible and it was not toxic at the concentrations used, TMC-2 may be a candidate novel therapeutic agent for rheumatoid arthritis.
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PMID:Dipeptidyl peptidase IV on activated T cells as a target molecule for therapy of rheumatoid arthritis. 1251 88

Several of the proinflammatory peptides involved in rheumatoid arthritis pathogenesis, including peptides induced downstream of tumor necrosis factor-alpha as well as the monocyte/T cell-attracting chemokines RANTES and stromal cell-derived factor (SDF)-1alpha 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.
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PMID:Dipeptidyl peptidase IV activity and/or structure homologs: contributing factors in the pathogenesis of rheumatoid arthritis? 1627 1


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