The anti-inflammatory effects of vitamin D in lung tissues

Research Project

Project/Area Number	16K09231
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	General internal medicine(including psychosomatic medicine)
Research Institution	The University of Tokyo
Principal Investigator	Ishii Masaki 東京大学, 医学部附属病院, 講師 (20724438)
Co-Investigator(Kenkyū-buntansha)	山口泰弘東京大学, 医学部附属病院, 講師 (60376473)
Research Collaborator	Isumi Kyoko Nakamura Tomomi Kanai Junko
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	ビタミンD / COPD / 炎症 / 肺の老化 / 高齢者 / ビタミンD受容体 / 肺の炎症 / サイトカイン / 内科 / 老化
Outline of Final Research Achievements	Vitamin D insufficiency is increasingly recognized as a prevalent problem worldwide, especially in patients with COPD. Previous studies have shown that COPD leads to low vitamin D levels, which further increase the severity of COPD. Vitamin D homeostasis represents one of the most important factors that potentially determine the severity of COPD. Nonetheless, the mechanisms underlying the anti-inflammatory effects of vitamin D receptor (VDR) in lung tissues are still unclear. To investigate the anti-inflammatory effects of VDR, we generated transgenic mice that show lung-specific VDR overexpression(TG mice). The TG mice were used to study the expression patterns of proinflammatory cytokines using real-time polymerase chain reaction and immunohistochemistry. The TG mice had lower levels of T helper 1-related cytokines than wild-type mice did. VDR expression is an important factor that influences anti-inflammatory responses in lung tissues and is down-regulated by cigarette smoke.
Academic Significance and Societal Importance of the Research Achievements	日本には、500万人以上の慢性閉塞性肺疾患 (COPD)の患者がいると推定され、超高齢社会を迎えた現状で、今後も増え続けると予測されているが、その多くは未診断の状態で、十分な治療が受けられていないのが現状である。これまで、多くの気管支拡張薬の効果が大規模な臨床試験で実証されているが、いまだCOPDの進行とその慢性炎症を根本的に治癒させる方策はない。本研究では、ビタミンD受容体に焦点をあて、ビタミンD受容体過剰発現マウス作成により、ビタミンDによる肺組織の抗炎症効果を実証できた初めての成果であり、高齢者COPD患者におけるビタミンDの有益性が示唆されると考えられた。