Differential role of NADPH oxidase in autoimmune diseases
| Project/Area Number |
20K07294
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 48030:Pharmacology-related
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Matsumoto Misaki 京都府立医科大学, 医学(系)研究科(研究院), 助教 (80533926)
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| Co-Investigator(Kenkyū-buntansha) |
岩田 和実 京都府立医科大学, 医学(系)研究科(研究院), 講師 (60305571)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | NADPH oxidase / スーパーオキシド / 関節炎 / 自己免疫疾患 / リポポリサッカライド / リポ多糖 / 活性酸素 |
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| Outline of Research at the Start |
NADPH oxidaseはスーパーオキシドなどの活性酸素種を産生する酵素であり、その触媒サブユニットであるNOXには複数のアイソフォームが存在する。本研究では、免疫細胞におけるNOX1およびNOX2アイソフォームの相違点を明らかにし、自己免疫疾患の病態に関わる役割を解明する。本研究により抗酸化薬では実現できないNOXアイソフォーム特異的な治療戦略の開発につなげる。
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| Outline of Final Research Achievements |
Nox1 deficiency significantly suppressed the onset and severity of the LPS-induced exacerbation of collagen-induced arthritis in mice. Splenocytes from both genotypes showed similar Th1/Th17 responses at 2 weeks after the collagen immunization. On the other hand, intraperitoneal injection of LPS increased NOX1 mRNA in CD11b+ monocytes/macrophages as well as CD11c+ dendritic cells of the spleen. These results suggest that NOX1 is involved in the effector (inflammation) phase of the experimental arthritis, but not in the priming phase.
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| Academic Significance and Societal Importance of the Research Achievements |
NOX2/NADPH oxidaseの遺伝的機能欠損は自己免疫疾患の発症リスクを増大させる。このため自己免疫疾患におけるNOX2の抑制的役割は注目されているが、発現量で劣るNOX1についてはあまり解析が進んでいなかった。本研究は、NOX1はNOX2と異なり自己免疫疾患の発症に寄与することを初めて報告したものであり、免疫系細胞におけるNOX1の新しい役割を提起するものである。
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Report
(4 results)
Research Products
(5 results)
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[Journal Article] Bortezomib is an effective enhancer for chemical probe-dependent superoxide detection.2022
Author(s)
Matsumoto M, Sawada H, Iwata K, Ibi M, Asaoka N, Katsuyama M, Shintani-Ishida K, Ikegaya H, Takegami S, Umemura A, Yabe-Nishimura C.
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Journal Title
Front Med (Lausanne)
Volume: 9
Pages: 941180-941180
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] NOX1/NADPH oxidase is involved in the LPS-induced exacerbation of collagen-induced arthritis2021
Author(s)
Matsumoto M, Liu J, Iwata K, Ibi M, Asaoka N, Zhang X, Katsuyama M, Matsuda M, Nabe T, Scroder K, Yabe-Nishimura C.
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Journal Title
J Pharmacol Sci
Volume: 146 (2)
Issue: 2
Pages: 88-97
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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