| 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
|
| Resource |
| Human and Animal Cells |
CCRF-HSB-2(RCB0016) |
