Regulation of cytokine production through the receptors for lysophospholipid in mast cells
| Project/Area Number |
11670434
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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 | Gunma University |
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Principal Investigator |
ISHIZUKA Tamotsu M.D.Lecturer, First Department of Internal Medicine, Gunma University School of Medicine., 医学部, 助手 (50302477)
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| Co-Investigator(Kenkyū-buntansha) |
OKAJIMA Fumikazu Ph.D.Professor, Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, 生体調節研究所, 教授 (30142748)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Mast Cell / Cell Migration / Cytokine / p38 MAP Kinase / Rho-kinase / MAPKAP kinase / Protein Kinase Cμ / Antigen / 肥満細胞 / サイトカイン / protein kinase C / MAP Kinase |
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| Research Abstract |
We found that mast cells express receptors for lysophspholipid. However, we cannot find the evidence that lysophospholipid modulates IgE Fc receptor (FcεRI)-mediated cytokine production in mast cells. We expects one of protein kinase C (PKC) members, PKCμ, is involved in FcεRI-mediated C-Jun amino-terminal kinase (JNK) activation and cytokine production in mast cells because only PKC inhibitors which inhibit PKCμ abolish FcεRI-mediated JNK activation but not those which cannot inhibit PKCμ. Although an accumulation of mast cells within the epithelial layer of the mucosa is observed in patients with allergic rhinitis and bronchial asthma, the responsible chemotactic factors are undefined. We investigated whether mast cells sensitized with antigen-specific IgE migrate toward the antigen or not. MC/9 mast cells sensitized with anti-dinitrophenyl (DNP) IgE migrated toward DNP conjugated human serum albumin (DNP-HSA). This migration was directional, and the degree of migration was stronger
… More
than that of stem cell factor (SCF)-induced migration. Mouse bone marrow-derived cultured mast cells (BMMC) also migrated toward the antigen. The high-affinity IgE Fc receptor (FcεRI)-mediated migration was significantly inhibited by pretreatment of-the cells with Y-27632, a Rho-associated coiled-coil forming protein kinase (ROCK) inhibitor, or SB 203580, a p38 MAP kinase (p38 MAPK) inhibitor. Both p38 MAPK and MAPKAP kinase 2 were activated following aggregation of FcεRI, and activation of MAPKAP kinase 2 was almost completely inhibited by 10μM SB203580. Partial inhibition of MAPKAP kinase 2 by pretreatment with wortmannin or a low concentration of SB203580 was not enough to block mast cell migration. On the other hand, Y-27632 did not affect the activation of MAPKAP kinase 2. These results indicate that antigen works not only as a stimulant for allergic mediators from IgE-sensitized mast cells but also as a chemotactic factor for mast cells. Both p38 MAPK activation and Rho-dependent activation of ROCK may be required for FcεRI-mediated cell migration. Less
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(3 results)
Research Products
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