Reference - Detail
| RRC ID | 1279 |
|---|---|
| Author | Williams YN, Baba H, Hayashi S, Ikai H, Sugita T, Tanaka S, Miyasaka N, Kubota T. |
| Title | Dipeptidyl peptidase IV on activated T cells as a target molecule for therapy of rheumatoid arthritis. |
| Journal | Clin Exp Immunol |
| Abstract |
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. |
| Volume | 131(1) |
| Pages | 68-74 |
| Published | 2003-1-1 |
| DOI | 10.1046/j.1365-2249.2003.02020.x |
| PII | 2020 |
| PMID | 12519388 |
| PMC | PMC1808610 |
| MeSH | Arthritis, Rheumatoid / drug therapy* Arthritis, Rheumatoid / immunology Cell Division / drug effects Cells, Cultured Depression, Chemical Dipeptidyl Peptidase 4* / blood Enzyme Inhibitors / therapeutic use Humans Indoles / therapeutic use* Interleukin-2 / immunology Isoquinolines / therapeutic use* Leukocyte Common Antigens / blood Lymphocyte Activation* T-Lymphocytes / enzymology* T-Lymphocytes / immunology |
| IF | 3.532 |
| Times Cited | 24 |
| WOS Category | IMMUNOLOGY |
| Altmetric score |
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | CCRF-HSB-2(RCB0016) |