2019 Fiscal Year Final Research Report
Effect of MPO and NOX2 deficiency on sterile inflammation and cytokine expression
Project/Area Number |
17K08126
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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 |
Integrative animal science
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Research Institution | Yokohama City University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Keywords | 免疫 / 好中球 / マクロファージ / ミエロペルオキシダーゼ / NADPHオキシダーゼ |
Outline of Final Research Achievements |
Accumulation of neutrophils and macrophages is a critical event in the pathogenesis of lung inflammation. Myeloperoxidase (MPO) and phagocyte NADPH oxidase (NOX2) contribute to microbial killing. This study aimed to evaluate the effect of MPO deficiency and NOX2 deficiency on lung inflammation induced by zymosan and nonviable Candida. Mice deficient in these enzymes showed more severe pneumonia than wild-type, which exhibited higher lung concentrations of proinflammatory cytokines such as MIP-2 and KC. In vitro, dectin-1 contributed to the production of those cytokines, which was associated with an upregulation of ERK pathway. We also found that NOX2 deficiency exhibits severe thymic atrophy and resulting lymphopenia concomitant with enhanced neutrophilic inflammation in a zymosan-induced systemic inflammation model.
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Free Research Field |
免疫学
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Academic Significance and Societal Importance of the Research Achievements |
感染によって炎症が重篤化することは肺炎などでよく知られている。一方、病原体が検出されないにも関わらず炎症が進行することもあり、そのような病態はNOX2を欠損したヒトにおいても知られている。しかし、感染非依存的な炎症の進行は発症機構が不明なため治療法に乏しい。本研究は、原因不明の炎症性疾患発症における食細胞機能異常のリスクを知るという基礎研究としての意義がある。
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