Effect of environmental chemicals on the Th1/Th2 development and exacerbation of airway hyperresponsiveness
| Project/Area Number |
15510046
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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 |
Risk sciences of radiation/Chemicals
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| Research Institution | Mie University |
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Principal Investigator |
KATO Takuma Mie University, Faculty of Medicine, Research Associate, 医学部, 助手 (60224515)
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| Co-Investigator(Kenkyū-buntansha) |
OIKAWA Saeko Mie University, Faculty of Medicine, Post Doctor Fellow, 医学部, 日本学術振興会特別研究員
及川 佐枝子(多田 佐枝子) 三重大学, 医学部, 日本学術振興会特別研究員
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Endocrine Disrupter / tributyltin / Th1 / Th2 / Asthma / IL-10 / IL-12 / allergy / 内分泌かく乱物質 / 免疫学 / 気道炎症 |
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| Research Abstract |
In this study, we have investigated the mechanisms of environmental chemicals to disturb Th1/Th2 balance. Here we show that environmental chemicals reduce intracellular GSH levels and forced increase in GSH levels by N-acetyl-L-Cysteine attenuate the effect of environmental chemicals to disturb Th1/Th2 development from naive CD4+ T cells. Furthermore, using one of the notable pollutant, TBT, we show that Th1 clones were more susceptible than Th2 clones to the TBT-induced apoptosis as defined by Annexin V binding to phosphatidylserine residues. Flow cytometry showed that Th1 clones generated higher level of intracellular H_2O_2 in response to TBT treatment than Th2 clones. An inverse correlation between basal levels of intracellular GSH and TBT-induced increase in H_2O_2 generation was observed. These results suggest that TBT more easily induce Th1 apoptosis via generation of ROS, due to the low GSH level, and that TBT may contribute to the amplification of Th2-predominance. We presume that lower basal levels of GSH in Th1 cells are important factors that determine the susceptibility of Th1 cells to TBT induced apoptosis. Based on the data we have presented here and previously, we propose a novel mechanism by which the environmental pollutants contribute to the increased prevalence of allergic diseases by induction of Th2 predominance via selective induction of apoptosis in differentiated Th1 cells as well as modulation of Th1/Th2 differentiation from naive CD4+ T cells.
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Report
(3 results)
Research Products
(25 results)
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[Journal Article] Definition of target antigens for naturally occurring CD4+CD25+ regulatory T cells.2005
Author(s)
Nishikawa, H., T.Kato, I.Tawara, K.Saito, H.Ikeda, K.Kuribayashi, P.M.Allen, R.D.Schreiber, S.Sakaguchi, L.J.Old, H.Shiku
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Journal Title
Journal of Experimental Medicine 201
Pages: 681-685
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Accelerated chemically-induced tumor development mediated by CD4+CD25+ regulatory T cells in wild type hosts.2005
Author(s)
Nishikawa, H., T.Kato, I.Tawara, T.Takemitsu, K.Saito, L.Wang, Y.Ikarashi, H.Wakasug, T.Nakayama, M.Taniguch, K.Kuribayashi, L.J.Old, H.Shiku
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Journal Title
Proceedings of the Natural Academy of Science, USA (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] CD4+CD25+ T cells responding to serologically defined autoantigens suppress antitumor immune responses.2003
Author(s)
Nishikawa, H., T.Kato, K.Tanida, A.Hiasa.H.Ikeda, Y.Ikarashi, H.Wakasugi, M.Kronenberg, T.Nakayama, M.Taniguchi, K.Kuribayashi, L.J.Old, H.Shiku
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Journal Title
Proceedings of the Natural Academy of Science, USA 100
Pages: 10902-10906
Description
「研究成果報告書概要(欧文)」より
Related Report
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