2000 Fiscal Year Final Research Report Summary
Regulation of neutrophil apoptosis in rheumatoid arthritis
| Project/Area Number |
10670423
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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 | KITASATO UNIVERSITY |
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Principal Investigator |
AKAHOSHI Tohru Kitasato Univ.School of Medicine, Department of Internal Medicine, Assistant Professor, 医学部, 講師 (70159325)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Sumiaki MD, Kitasato Univ.School of Medicine, Department of Internal Medicine, Research Associate, 医学部, 助手 (80265595)
HOSAKA Shigeru MD, Kitasato Univ.School of Medicine, Department of Internal Medicine, Assistant Professor, 医学部, 講師 (80209220)
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| Project Period (FY) |
1998 – 2000
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| Keywords | rheumatoid arthritis / neutrophils / apoptosis / PGE_2 |
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| Research Abstract |
Infiltration of neutrophils into the inflamed joints is a characteristic feature of rheumatoid arthritis (RA). Accumulated neutrophils play pivotal roles on destruction of the inflamed joints through the elaboration of inflammatory mediators. Neutrophils are short-lived cells and spontaneously die by apoptosis. A number of factors have been shown to modulate spontaneous neutrophil apoptosis. However, the regulatory mechanisms of neutrophil apoptosis in RA have not been elucidated. We investigated the regulatory roles of synovial cell-derived-factors and various anti-rheumatic drugs on neutophil apoptosis. The results obtained in this study are as following. (1) Pro-inflammatory cytokines (IL-1, TNF-α) produce soluble factor (s) capable of inhibiting spontaneous neutrophil apoptosis. (2) GM-CSF is a major factor for this activity. (3) A novel inhibitory factor for neutrophil apoptosis (MW about 25 Kd) has been found. (4) PGE2 prevented neutrophil apoptosis through the binding to the receptors (EP4 and EP2) on neutrophils. On the other hand, EP3 agonist rapidly promoted unique death of neutrophils resembling to apoptosis. (5) Among the anti-rheumatic drugs examined, sulfasalazine rapidly promoted neutrophil apoptosis and lipophilic gold complex (auranofin) also modulated cellular death. These findings indicate that joint inflammation potentially elongates neutrophil survival by inhibiting apoptosis and the drugs used in the treatment of RA promote neutrophil death by inducing apoptosis.
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[Publications] Nishimura, A., Akahoshi, T., Takahashi, M., Takagishi, K., Itoman M., Kondo, H., Takahashi, Y., Yokoi, K., Mukaida, N., and Matsushima, K.: "Attenuation of monosodium urate crystal-induced arthritis in rabbits by a neutralizing antibody against interleukin-8."J.Leuko.Biol.. 62. 444-449 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Hosaka, S., Uchiyama, M., Ishikawa, M., Akahoshi, T., Kondo, H., Shimauchi, C., Sasahara, T., Inoue, M.: "Yersinia enterocolitica serotype O : 8 septicemia in an otherwise healthy adult : analysis of chromosome DNA pattern by pulse-field gel electrophoresis."J.Clin.Microbiol.. 35. 3346-3347 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Liu, J., Akahoishi, T., Sasahara, T., Kitasato, H., Namai, R., Sasaki, T., Inoue, M., Kondo, H.: "Inhibition of neutrophil apoptosis by verotoxin 2 derived from Escherichia coli O157 : H7."Infect.Immun.. 67. 6203-6205 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Liu, J., Akahoshi, T., Jiang, S., Namai, R., Kitasato, H., Endo, H., Kameya, T., Kondo, H.: "Induction of neutrophil death resembling neither apoptosis nor necrosis by ONO-AE-248, a selective agonist for PGE2 receptor subtype 3."J.Leuko.Biol.. 68. 187-193 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Liu, J., Akahoshi, T., Namai, R., Matsui, T., Kondo, H.: "Effect of auranofin, an antirheumatic drug, on neutrophil apoptosis."Inflamm.Res.. 49. 445-451 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Matsui, T., Akahoshi, T., Namai, R., Hashimoto, A., Kurihara, Y., Rana, M., Nishimura, A., Kitasato, H., Endo, H., Kondo, H.: "Selective recruitment of CCR6 expressing cells by increased production of MIP-3α in rheumatoid arthritis."Clin.Exp.Immunol.. (In press).
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「研究成果報告書概要(欧文)」より
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[Publications] Akahoshi, T., Ishikawa, M., Takahashi, M., Sekiyama, N., Hasegawa, K., Watanabe, K., Ishihara, Y., Kondo, H.: "A case of systemic lupus erythematosus complicated with progressive multifocal leukoencephalopathy : Case report and review of the literature."Jap.J.Rheumatol.. 7. 55-60 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Tanaka, S., Akahoshi, T., Kamimura, A., Hosaka, S., Endo, H., Kanamori, A., Ohbu, M., Kondo, H.: "A case of primary Sjogren syndrome complicated by Graves's disease and primary biliary cirrhosis."Jap.J.Rheumatol.. 9. 101-106 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Uchiyama, M., Akahoshi, T., Matsui, T., Watabe, H., Koredo.K., Tanaka, S., Matsuo, T., Tatsumi, H., Kamata, K., Kobayashi, Y., Kondo, H.: "Crescentic glomerulonephritis with anti-myeloperoxidase antibodies developing during the course of IgA nephropathy in a patient with rheumatoid arthritis."Modern Rheumatol.. 11. 76-79 (2001)
Description
「研究成果報告書概要(欧文)」より
