Roles of G-protein coupled receptors in inflammation and immunity.
| Project/Area Number |
16390090
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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 |
Pathological medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YOKOMIZO Takehiko The University of Tokyo, Graduate school of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (60302840)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2005: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2004: ¥9,200,000 (Direct Cost: ¥9,200,000)
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| Keywords | Arachidonic acis / leukotriene B4 / receptor deficient mice / cytokines / bronchial asthma / delayed-type hyperreactivity / pH sensor |
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| Research Abstract |
Based on the finding that leukotriene B_4 receptor 1 (BLT1) is expressed highly in Th2 lymphocytes, we analyzed the roles of BLT1 using an ovalbumin-induced bronchial asthma model. BLT1-null mice did not develop airway hyperresponsiveness, eosinophilic inflammation and hyperplasia of goblet cells. Attenuated symptoms were accompanied by reduced IgE production, and accumulation of IL-5 and IL-13 in bronchoalveolar lavage fluid, suggesting attenuated Th2-type immune response in BLT1-null mice. Peribronchial lymph node cells of sensitized BLT1-null mice showed much attenuated proliferation and production of Th2 cytokines upon re-stimulation with antigen in vitro. Thus, LTB_4-BLT1 axis is required for the development of Th2-type immune response, and blockade of LTB_4 functions through BLT1 would be novel and useful in the effort to ameliorate bronchial asthma and related Th2-biased immune disorders.
Dendritic cells (DCs) are important antigen-presenting cells that control Th1- and Th2-type
… More
immunological reactions by releasing cytokines and interacting directly with T cells. We found that BLT1 is expressed in human monocyte-derived DCs and mouse bone marrow-derived DCs (BMDCs). Detailed analyses using BMDCs revealed that BLT1-deficient DCs produced less IL-l2 p70 than WT DCs, leading to attenuated IFN-□ production in an allogeneic mixed lymphocyte reaction. Adoptive transfer of BLT1-deficient DCs into naive WT mice induced a weakened. Th1 response and an enhanced Th2 response in vivo compared to WT DCs. BLT1-deficient mice consistently showed much attenuated delayed-type hypersensitivity (DTH), in which Th1-type cellular responses play a key role, and popliteal lymph node cells of BLT1-deficient mice showed reduced production of Th1 cytokines after DTH induction compared to cells from WT mice. Thus, in addition to its role in inflammation, the LTB4-BLT1 axis is important in initiating Th1-type immunological reactions mediated by DCs.
We characterized G2A receptor, which was reported as a lysophospholipid receptor, as a proton-sensing GPCR. Less
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Report
(3 results)
Research Products
(40 results)
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[Journal Article] Characterization of a mouse second leukotriene B4 receptor, mBLT2.2005
Author(s)
Iizuka, Y., Yokomizo.T., Terawaki, K., Komine, M., Tamaki, K., Shimizu, T.
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Journal Title
J.Biol.Chem. 280
Pages: 2129-2123
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Synthesis of 2-, 4- and 5-(2-alkylcarbamoyl-1-methylvinyl)-7-alkyloxybenzo[b]furans and their leukotriene B(4) receptor antagonistic activity.2005
Author(s)
Ando K, Tsuji E, Ando Y, Kunitomo J, Kobayashi R, Yokomizo T, Shimizu T, Yamashita M, Ohta S, Nabe T, Kohno S, Ohishi Y.
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Journal Title
Org.Biomol.Chem. 3
Pages: 32129-32139
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Differential Expression of S100A2, S100A4 in Lung Adenocarcinomas : Clinicopathologic Significance, Relationship to p53, and Identification of Their Target Genes.2005
Author(s)
Matsubara D, Niki T, Ishikawa S, Goto A, Ohara E, Yokomizo T, Heizmann C W, Aburatani H, Moriyama S, Moriyama H, Nishimura Y, Funata N, Fukayama M.
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Journal Title
Cancer Sci. 96
Pages: 844-857
NAID
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] (2004) Preparation of 2- and 4-(2-alkylcarbamoyl-1-methylvinyl)-7-alkyloxybenzo[b]furans having potent atagonistic activity against human leukotriene B4 BLT1 and/or BLT2 receptors.2004
Author(s)
Ando, K., Tsuji, E., Ando, Y, Kunitomo, J., Yamashita, M., Ohta, S., Nabe, T., Kohno, S., Yokomizo, T., Shimizu, T., Ohishi, Y.
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Journal Title
Org.Biomol.Chem. 2
Pages: 3427-3431
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Attenuation of folic acid-induced renal inflammatory injury in platelet-activating factor receptor-deficient mice.
Author(s)
Doi, K., Okamoto, K., Negishi, K., Suzuki, Y., Nakao, A., Fujita, T., Toda, A., Yokomizo, T., Kita, Y, Kihara, Y., Ishii, S., Shimizu, T., Noiri, E.
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Description
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