The role of MAPK regulation by TLR signaling in bacterial infection.
| Project/Area Number |
17390128
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Kyushu University |
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Principal Investigator |
YOSHIKAI Yasunobu Kyushu University, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (90158402)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2006: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2005: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Keywords | dual specificity phosphatase / Th1 / Th2 / Listeria / BCG / cytokine / JNK / MAPキナーゼ / TH1 / TH2 / JNK特異的脱リン酸化酵素 / リステリア / 細菌感染 / Tgマウス / アレルギー |
|---|
| Research Abstract |
We have previously isolated a cDNA encoding a novel mitogen-activated protein kinases phosphatase (MKPM/DUP16) from LPS-stimulated mouse macrophages. Here we found that DUP16 was preferentially expressed by activated Th2 cells in addition to LPS-stimulated macrophages. To elucidate the potential role of DUP16 in Th1/Th2 differentiation, we generated transgenic mice expressing wild type of DUP16 (WTDUP16) or dominant negative from of DUP16 (DNDUP16) selectively in T cells under the control of lck promoter. Both WTDUP16Tg and DNDUP16Tg mice exhibited normal T cell development in thymus and peripheral lymphoid tissues. Naive T cells from WTDUP16 Tg mice produced less level of IL-4 in response to immobilized anti-CD3 and CD28 mAbs, whereas those from DNDUP16Tg mice produced higher level of IL-4 upon TCR triggering. DUP16Tg mice showed resistance to Listeria moncytogenes or Mycobacterium bovis (BCG) infection accompanied by enhanced Th1 responses, whereas DNDUP16Tg mice showed impaired host desense against L.monocytogenes or BCG infection accompanied by impaired Th1 responses. T cells from WTDUP16Tg mice with showed impaired Th2 response after sensitized with OVA. DO11.10(OVA323-339/Ad-specific TCR) Tg x DUP16Tg mice produced less level of IL-4 in response to various doses of OVA peptide in vitro. These results suggest that overexpression of DUP16 may block JNK activation and inhibit early Th2 cells responses, resulting in augmentation of Th1 responses, whereas suppression of endogenous DUP16 activity by DNDSP16 may prolong JNK activation and enhance early Th2 responses, resulting in impairment Th1 responses. Thus, DUP16 may play an important role in regulation of Th2 response via regulation of JNK activity.
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Report
(3 results)
Research Products
(73 results)
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[Journal Article] Levan (β-2,6-fructan), a major fraction of fermented soybean mucilage, displays immunostimulating properties via Toll-like receptor 4 signaling : Induction of IL-12 production and suppression of Th2 response with IgE production.2006
Author(s)
Xu Q., Yajima, T., Li, W, Saito K., Fushimi, T., Ohshima, Y, Tsukamoto, Y., Yoshikai, Y.
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Journal Title
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Pages: 96-101
Description
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[Journal Article] Regulatory roles of NKT cells in the induction and maintenance of cyclophosphamide-induced tolerance2006
Author(s)
Iwai, T., Tomita Y., Shimizu I., Yasunami Y., Kajiwara T., Okano S., Yoshikai Y., Taniguchi M., Nomoto K., Yasui H.
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Journal Title
J.Immunol. 177
Pages: 8400-9
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[Journal Article] A novel model system for renal cancer treatment with low levels of mixed chimerism by nonmyeloidablative allogeniec hematopoietic cell transplantation in combination with cyclophosphamide in mice.2005
Author(s)
Harano, M., Eto, M., Iwai T., Tasugami K., Kiyoshima K., Tsuneyoshi, M., Yoshikai Y., Naito S.
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