2003 Fiscal Year Final Research Report Summary
Basic study concerning the gene therapy using p53 gene toward rheumatoid arthritis
| Project/Area Number |
14570419
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | NHO Nagasaki Medical Center |
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Principal Investigator |
MIGITA Kiyoshi NHO Nagasaki Medical Center Clinical Research Center, Department of Immunology, Director, 免疫研究部長 (60264214)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Rheumatoid arthritis / Mitogen-activated protein kinase / p53 / leflunomide / matrixmetalloproteincese / tacrolimus |
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| Research Abstract |
Leflunomide is an immuneregulatory drug that has shown effectiveness in the prevention of organ graft rejection as well as in an array of autoimmune diseases. In order to explore the mechanism of leflunomide-mediated immunosuppression, we investigated the effects of leflunomide on antigen-stimulated T cells in vivo. Leflunomide induced p53 expression in SEB-activated V□8^+ T cells. Also, increased levels of proliferating cell nuclear antigen (PCNA) and Cyclin E expression of SEB-activated V□8^+ T cells was suppressed by leflunomide. Our data suggest that the leflunomide-mediated cell cycle regulation of activated T cells may present a potential mechanism of immunosuppression achieved by leflunomide treatment. We also investigated the effects of A77 1726, leflunomide's active metabolite, on mitogen-activated protein kinases (MAPK) activation in IL-1β-stimulated rheumatoid synovial fibroblasts. The effects of A77 1726 on the secretion of matrix metalloproteinases (MMPs) from rheumatoid synovial fibroblasts were also examined. A77 1726 partially A77 1726 efficiently suppressed IL-1β-stimulated rheumatoid synovial fibroblasts. Our results suggest that the suppression of MAPK signaling pathway and MMPs synthesis in rheumatoid synovial fibroblats is a possible mechanism for the inhibitory activity of leflunomide against rheumatoid arthritis.
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[Publications] Tanaka F, Migita K, Honda S, Fukuda T, Mine M, Nakamura T, Yamasaki S, Ida H, Kawakami A, Origuohi T, Eguchi K: "Clinical outcome and survival of secondary (AA) amyloidosis."Clin Exp Rheumatol. 21. 343-346 (2003)
Description
「研究成果報告書概要(和文)」より
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[Publications] Ida H, Nakashima T, Kedersha NL, Yamasaki S, Huang M, Izumi Y, Miyashita T, Origuchi T, Kawakami A, Migita K, Bird PI, Anderson P, Eguchi K: "Granzyme B leakage-induced cell death : a new type of activation-induced natural killer cell death."Eur J Immunol. 33. 3248-3292 (2003)
Description
「研究成果報告書概要(和文)」より
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[Publications] Miyashita T, Kawakani A, Tamai M, Izumi Y, Mingguo H, Tanaka F, Abiru S, Nakashima K, Iwanaga N, Aratake K, Kamachi M, Arima K, Ida H, Migita K, Origuchi T, Tagashira S, Nishikaku F, Eguchi K: "Akt is an endogenous inhibitor toward tumor necrosis factor-related apoptosis inducing ligand-mediated apoptosis in rheumatoid synovial cells."Biochem Biophys Res Commun. 312. 397-404 (2003)
Description
「研究成果報告書概要(和文)」より
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[Publications] Nakashima K, Kawakami A, Hida A, Yamasaki S, Nakamura H, Kamachi M, Miyashita T, Tanaka F, Izumi Y, Tamai M, Ida H, Furuyama M, Koji T, Nakamura T, Migita K, Origuchi T, Eguchi K.: "Protection of mitochondrial perturbation by human T-lymphotropic virus type 1 tax through induction of Bcl-xL expression."J Lab Clin Med. 142. 341-347 (2003)
Description
「研究成果報告書概要(和文)」より
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[Publications] Kawakami A, Urayama S, Yamasaki S, Hida A, Miyashita T, Kamachi M, Nakashima K, Tanaka F, Ida H, Kawabe Y, Aoyagi T, Furuichi I, Migita K, Origuchi T, Eguchi K: "Anti-apoptogenic function of TGFbeta1 for human synovial cells : TGFbeta1 protects cultured synovial cells from mitochondrial perturbation induced by several apoptogenic stimuli."Ann Rheum Dis. 63. 95-97 (2004)
Description
「研究成果報告書概要(和文)」より
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[Publications] Fumimori T, Honda S, Migita K, Hamada M, Yoshimuta T, Honda J, Fukuda T, Suzuki R, Gotoh M, Eguchi K, Aizawa H.: "Erythromycin suppresses the expression of cyclooxygenase-2 in rheumatoid synovial cells."J Rheumatol. 31. 436-441 (2004)
Description
「研究成果報告書概要(和文)」より
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[Publications] Kiyoshi Migita, Taichiro Miyashita, Hiromi Ishibashi, Yumi Maeda, Minoru Nakamura, Hiroshi Yatsuhashi, Hiroaki Ida, Atsushi Kawakami, Takahiko Aoyagi, Yojiro Kawabe, Katsumi Eguchi: "Suppressive effect of leflunomide metabolite (A77 1726) on metalloproteinases production in IL-1 stimulated rheumatoid synovial fibroblasts"Clin Exp Immunol. (in press).
Description
「研究成果報告書概要(和文)」より
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[Publications] Tanaka F, Migita, K, Honda S, Fukuda T, Mine M, Nakamura T, Yamasaki S, Ida H, Kawakami A, Origuchi T, Eguchi K: "Clinical outcome and survival of secondary (AA) amyloidosis."Clni Exp Rhematol. 21. 343-346 (2003)
Description
「研究成果報告書概要(欧文)」より
-
-
[Publications] Ida H, Nakashima T, Kedersha NL, Yamasaki S, Huang M, Izumi Y, Miyashita T, Origuchi T, Kawakami A, Migita K, Bird PI, Anderson P, Eguchi K: "Granzyme B leakage-induced cell death : a new type of activation-induced matural killer cell death."Eur J Immunol.. 33. 3248-3292 (2003)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Miyashita T, Kawakami A, Tamai M, Izumi Y, Mingguo H, Tanaka F, Abiru S, Nakashima K, Iwanaga N, Aratake K, Kamachi M, Arima K, Ida H, Migita K, Origuchi T, Tagashira S, Nishikaku F, Eguchi K: "Akt is an endogenous inhibitor toward tumor necrosis factor-related apoptosis inducing ligand-mediated apoptosis in rheumatoid synovial cells."Biochem Biophys Res Commun. 312. 397-404 (2003)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Nakashima K, Kawakami A, Hida A, Yamasaki S, Nakamura H, Kamachi M, Miyashita T, Tanaka F, Izumi Y, Tamai M, Ida H, Furuyama M, Koji T, Nakamura T, Migita K, Origuchi T, Eguchi K: "Protevtion of mitochondrial perturbation by human t-lymphotropic virus type 1 tax through induction of Bcl-xL expression."J Lab Clin Med. 142. 341-347 (2003)
Description
「研究成果報告書概要(欧文)」より
-
-
[Publications] Kawakami A, Urayama S, Yamasaki S, Hida A, Miyashita T, Kamachi M, Nakashima K, Tanaka F, Ida H, Kawabe Y, Aoyagi T, Furuichi I, Migita K, Origuchi T, Eguchi K: "Anti-apoptogenic function of TGFbetal for human synovial cells : TGFbetal protects cultured synovial cells from mitochondrial perturbation induced by several apoptogenic stimli."Ann Rheum Dis. 63. 95-97 (2004)
Description
「研究成果報告書概要(欧文)」より
-
-
[Publications] Fumimori T, Honda S, Migita K, Hamada M, Yoshimuta T, Honda J, Fukuda T, Suzuki R, Gotoh M, Eguchi K, Aizawa H: "Erythromycin suppresses the expression of cyclo-oxygenase-2 in rheumatoid synovial cells."J Rheumatol. 31. 436-441 (2004)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kiyoshi Migita, Taichiro Miyasita, Hiromi Ishibashi, Yumi Maeda, Minoru Nakamura, Hiroshi Yatsuhashi, Hiroaki Ida, Atsushi Kawakami, Takahiko Aoyagi, Yojiro Kawabe, Katsumi Eguchi: "Suppressive effect of leflunomide metabolite (A77 1726) on metalloproteinases production in IL-1 stimulated rheumatoid synovial fibroblasts."Clin Exp Immunol. (in press).
Description
「研究成果報告書概要(欧文)」より
