Novel regulatory mechanism of human Toll-like receptor 4 function by the inhibitory monoclonal antibody
| Project/Area Number |
24790112
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Drug development chemistry
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| Research Institution | Tohoku University (2013)
Saga University (2012) |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | TLR4 / MD-2 / リポ多糖 / モノクローナル抗体 / 敗血症 / 抗体医薬 / 免疫学 |
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| Research Abstract |
In this study, novel inhibitory monoclonal antibodies against human Toll-like receptor 4 (TLR4), which are potential leading antibodies for anti-sepsis antibody drugs, were developed. These antibodies inhibited the production of proinflammatory cytokines, the upregulation of costimulatory molecules and the activation of NF-kappaB in lipopolysaccharide (LPS)-stimulated cells such as human peripheral blood mononuclear cells. The inhibitory activities were mediated by novel mechanism that is the induction of inactive TLR4 oligomerization, the inhibition of LPS-induced TLR4 internalization, but not the inhibition of TLR4-LPS binding. In addition, the epitope to which the binding of antibody inhibits the TLR4 function was found on extracellular domain of TLR4 independently of MD-2. Identification and chracterization of this epitope may provide a promising drug discovery target sturucture for the development of anti-septic antibody drugs.
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Report
(3 results)
Research Products
(31 results)
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[Journal Article] Deficiency of CD73/ecto-5'-nucleotidase in mice enhances acute graft-versus-host disease2012
Author(s)
Tsukamoto H, Chernogorova P, Ayata K, Gerlach UV, Rughani A, Ritchey JW, Ganesan J, Follo M, Zeiser R, Thompson LF, Idzko M
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Journal Title
Blood
Volume: 119(19)
Issue: 19
Pages: 4554-4564
DOI
Related Report
Peer Reviewed
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[Book] Handbook of Glycosyltransferases and Related Genes, Mannosyl (β-1,4-)-glycoproteinβ-1,4-N-acetylglucosaminyltransferase (MGAT3);β1,4-N-Acetylglucosaminyltransferase III (GnT-III, GlcNAc-T III)(Taniguchi N, Honke K, Fukuda M, Narimatsu H, Yamaguchi Y, Angata T, eds)2014
Author(s)
Ikeda Y, Ihara H, Tsukamoto H, Gu J, Taniguchi N
Publisher
Springer Japan (Tokyo, Japan)
Related Report
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[Book] Handbook of Glycosyltransferases and Related Genes(FUT8), Fucosyltransferase 8. GDP-fucose N-glycan coreα6-fucosyltransferase(Taniguchi N, Honke K, Fukuda M, Narimatsu H, Yamaguchi Y, Angata T, eds)2014
Author(s)
Ihara H, Tsukamoto H, Gu J, Miyoshi E, Taniguchi N, Ikeda Y
Publisher
Springer Japan (Tokyo, Japan)
Related Report
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