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Role of Bruton's tyrosine kinase in allergic reactions

Research Project

Project/Area Number 10672045
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionGifu Pharmaceutical University

Principal Investigator

INAGAKI Naoki  Gifu Pharmaceutical University, lecturer, 医学部, 助教授 (30137062)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsBruton's tyrosine kinase / Btk / IgE / allergic reaction / XID mouse / Bruton's tyrosine kinase / Btk / XIDマウス / ブルトン型チロシンキナーゼ / CBA / Nマウス / XID
Research Abstract

To elucidate the role of Bruton's tyrosine kinase (Btk) in allergic reactions, we investigated some experimental allergic reactions in CBA/N (XID) mice and CBA/JxCBA/N F1 male mice comparing to their control mice, CBA/J and CBA/JxCBA/N F1 female mice. Furthermore, antisense oligonucleotide was employed to examine the role of Btk in mediator release from cultured human mast cells.
All three phases of dinitrofluorobenzene-induced IgE-dependent triphasic cutaneous reaction was reduced in CBA/JxCBA/N F1 male mice comparing to female mice. IgM production in CBA/N mice induced by ovalbumin immunization was apparently low in comparison with CBA/J mice, whereas IgE production was apparently high in CBA/N mice. There was no difference between CBA/J and CBA/N mice in production of proinflammatory cytokines, TNF-α, IL-1β and Il-6, caused by treatments with Propionibacterium acnes and lipopolysaccharide.
Cultured human mast cells release histamine, leukotrienes, prostaglandins and cytokines after IgE-dependent stimulation. In the present study, we treated cultured human mast cells with antisense oligonucleotide for a week before the stimulation. Histamine release and GM-CSF production were not affected by the treatment. In the present experimental condition, antisense oligonucleotide might not be introduced into mast cells effectively. We need additional experiments using different experimental conditions.
These results and previous data obtained last year suggest that IgE-dependent allergic reactions wane in XID mice because of inadequate activation of mast cells. Btk may not contribute the activation of cells of macrophage lineage. Furthermore, cutaneous reaction caused by repeated application with hapten and IgE production may be regulated by Btk, because these responses are increased in XID mice.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Shichijo M. et al.: "The effect of anti-asthma drugs on mediator release from cultared human mast cells"Clin. Esp. Allergy. 28. 1228-1236 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawatami Y. et al.: "Terreic acid, a quinone epoxide inhibitor of Bruton's tyrosine kinase"Proc. Natl. Acad. Sci USA. 96. 2227-2232 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kimata M. et al.: "Ca^<2+> and protein kinase C signaling for histamine and swfido leukotrienes released from human cultured mast cells"Biochem. Biophys. Res. Commun.. 257. 895-800 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shichijo M. et al.: "Role of cyclic 3',5'-adenosine monophosphate in the regulation of chemical mediator releass and cytokine production From cultured human mast cells"J. Allergy Clin. Immunol.. 103. s421-s428 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 稲垣直樹 他: "培養ヒト肥満細胞を用いた抗アレルギー薬の評価"臨床検査. 43. 767-774 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shichijo M, Inagaki N, Nakai N, Kimata M, Nakahata t, Serizawa I, Iikura Y, Saito H, Nagai H: "The effect of anti-asthma drugs on mediator release from cultured human mast cells."Clin Exp Allergy. 28. 1228-1236 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawakami Y, Hartman SE, Kinoshita E, Suzuki H, Kitaura J, Yao L, Inagaki N, Franco A, Hata D, Maeda-Yamamoto M, Fukamachi H, Nagai H, Kawakami T: "Terreic acid, a quinone epoxide inhibitor of Bruton's tyrosine kinase"Proc Natl Acad Sci USA. 96. 2227-2232 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kimata M, Shichijo M, Miura T, Serizawa I, Inagaki N, Nagai H: "CaィイD12+ィエD1 and protein kinase C signaling for histamine and sulfidoleukotrienes released from human cultured mast cells."Biochem Biophys Res Commun. 257. 895-900 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shichijo M, Inagaki N, Kimata M, Serizawa I, Saito H, Nagai H: "Role of cyclic 3', 5'-adenosine monophosphate in the regulation of chemical mediator release and cytokine production from cultured human mast cells."J Allergy Clin Immunol. 103. S421-S428 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shichijo M. et al.: "The effect of anti-asthma drugs on mediator release from cultured human mast cells"Clin.Exp.Allergy. 28. 1228-1236 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawakami Y. et al.: "Terreic acid,a quinone epoxide inhibitor of Bruton's tyrosine kinase"Proc.Natl.Acad.Sci.USA. 96. 2227-2232 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kimata M. et al.: "Ca^<2+> and protein kinase C signaling for histamine and sulfidoleuko Trienes released From human cultured mast cells"Biochem.Biophys.Res.Commun.. 257. 895-900 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shichijo M. et al.: "Role of cyclic 3',5'-adenosine monophosphate in the regutation of chemical mediator release and cytokine production from cultured human mast cells"J.Allergy Clin.Immunol.. 103. S421-S428 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 稲垣 直樹 他: "培養ヒト肥満細胞を用いた抗アレルギー薬の評価"臨床検査. 43. 767-774 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hata D et al: "Involvement of Bruton's Tyrosine Kinase in FceRI-dependent mast cell degranulation and cytokine produetion." Journal of Experimental medicine. 187(8). 1235-1247 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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