The anti-inflammatory effects of vitamin D in lung tissues

2018 Fiscal Year Final Research Report

• 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
• Keywords: ビタミンD / COPD / 炎症

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.

Free Research Field

老年医学、呼吸器内科学

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。