| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Noriyoshi Kanazawa Univ., Faculty of Medicine, Research Associate, 医学部, 助手 (50242524)
SUDO Katsuko Tokyo Univ., Inst. Med. Sci., Research Associate, 医科学研究所, 助手 (50126091)
IWAKURA Yoichiro Tokyo Univ., Inst. Med. Sci., Professor, 医科学研究所, 教授 (10089120)
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| Research Abstract |
IL-1 α, IL-1 β, IL-Ira KO and IL-1 α/β double KO mice were generated to elucidate pleiotropic function of IL-1 in an animal body, and roles of IL-1 in immune and stress responses were clarified as described below.
(1) IL-1 β , but not IL-1 α, is crucial in terpentine-induced fever development and glucocorticoid secretion.
(2) Inflammation induced by apoptosis inducer Fas ligand is mediated by IL-1 β which is released by caspase 1 independent mechanism.
(3) Chronic inflammatory arthropathy resembling rheumatoid arthritis is spontaneously developed in IL-Ira KO mice on a BALB/c background.
(4) LPS-induced HIV-1 expression in transgenic mice is mediated by TNF α and IL-1.
(5) In collaboration with other laboratories, apoptosis in neural cells caused by ischaemia and apoptosis in germ cells caused by loss of ataxia telangiectasia-mutated (Atm) gene function are mediated by IL-1β.
(6) T cell-dependent antibody production is regulated by IL-1 β, but not by IL-1 α, through induction of CD40L and OX40 on T cells.
(7) IL-1α, but not IL-1β, is required for contact-allergen-specific T cell activation during the sensitization phase in contact hypersensitivity.
(8) Suppression of autoimmune arthritis in IL-1 KO mice in which T cell activation is impaired due to low levels of CD40 ligand and OX40 expression on T cells.
In support with the Grant-in-Aid for Scientific Research, various roles of IL-1 in fever development, stress response, antibody production, contact hypersensitivity, rheumatoid arthritis development and apoptosis of neural cells and germ cells were elucidated. These results and our IL-1 genes KO mice could be very useful to understand the mechanism of IL-1-mediated human diseases and to develop medical treatment for them.
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