The mechanism of innate inflammation in response to cell death and it's contribution to the pathogenesis of rheumatoid arthritis
Project/Area Number |
23591468
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
膠原病・アレルギー・感染症内科学
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Research Institution | Teikyo University |
Principal Investigator |
KONO Hajime 帝京大学, 医学部, 准教授 (60585074)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
|
Keywords | 自然炎症 / IL-1 / Cathepsin C / Caspase 1 / 細胞死 / インフラマソーム / 結晶 / 自然免疫 / 炎症 |
Research Abstract |
Cell death, especially necrotic cell death, induces acute inflammation. It is supposed that this acute responses underlie many pathological conditions including autoimmune diseases, but the molecular mechanisms of the danger signals to evoke inflammation or the key pathways responsible for neutrophil recruitment are not well studied. We investigated the molecular mechanisms responsible for inducing inflammatory responses to necrotic cells in vivo. In our system the inflammation to cell death depends on IL-1. IL-1 is transcribed as an immature protein and requires cleavage by Caspase-1. Here we identified a novel molecular pathway to cell death-induced inflammation that is dependent on IL-1, but not on Caspase-1. IN addition, we identified Cathepsin C as one of the key molecules involved in this Caspase-1 independent pathway in vivo. Cathepsin C is known to maturate neutrophil serene proteases including proteinase 3 that was shown to have ability to maturate IL-1 in vitro.
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Human leukocyte antigens and systemic lupus erythematosus : A protective role for the HLA-DR6 alleles DRB1*13:02 and *14:032014
Author(s)
Furukawa H, Kawasaki A, Oka S, Ito I, Shimada K, Sugii S, Hashimoto A, Komiya A, Fukui N, Kondo Y, Ito S, Hayashi T, Matsumoto I, Kusaoi M, Amano H, Nagai T, Hirohata S, Setoguchi K, Kono H, Okamoto A, Chiba N, Suematsu E, Katayama M, Migita K, Suda A, Ohno S, Hashimoto H, Takasaki Y, Sumida T, Nagaoka S, Tsuchiya N, Tohma S
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Journal Title
PLoS One
Volume: 9
Issue: 2
Pages: 152-160
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF32014
Author(s)
De Nardo D, Labzin LI, Kono H, Seki R, Schmidt SV, Beyer M, Xu D, Zimmer S, Lahrmann C, Schildberg FA, Vogelhuber J, Kraut M, Ulas T, Kerksiek A, Krebs W, Bode N, Grebe A, Fitzgerald ML, Hernandez NJ, Williams BR, Knolle P, Kneilling M, Röcken M, Lütjohann D, Wright SD, Schultze JL, Latz E
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Journal Title
Nat Immunol
Volume: 15(2)(Epub 2013 Dec 8)
Issue: 2
Pages: 152-60
DOI
Related Report
Peer Reviewed / Open Access
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