The development of drug delivery system of carbon monoxide for inflammatory bowel disease

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09322
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Takagi Tomohisa 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (70405257)
• Co-Investigator(Kenkyū-buntansha): 内藤 裕二 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (00305575) ; 内山 和彦 京都府立医科大学, 医学(系)研究科(研究院), 助教 (50298428) ; 堅田 和弘 京都府立医科大学, 医学(系)研究科(研究院), 助教 (60593910)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Heme oxygenase-1 / 一酸化炭素 / 炎症性腸疾患

Outline of Final Research Achievements

In this project, we confirmed that heme oxygenase-1 (HO-1) is mainly expressed in macrophages in the inflamed colonic mucosa using the murine colitis model, and carbon monoxide (CO) produced from HO-1 directly regulates Th17 differentiation of lymphocytes, and CO regulated the gut environment by augmenting clearance of enteric microbes. In addition, the rectal administration of a CO-saturated solution protected the intestinal mucosa from inflammation and accelerated colonic ulcer healing through enhanced epithelial restoration. These data suggested that CO could be a novel therapeutic molecule in patients with inflammatory bowel disease, including ulcerative colitis and Crohn’s disease.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

難治性・再発性疾患である炎症性腸疾患に対する病態解明・新規治療法の開発は重要な課題であり、本研究により抗酸化酵素HO-1(heme oxygenase-1)が抗原提示細胞（マクロファージ）に発現し、生成する一酸化炭素(carbon monoxide: CO)を介してリンパ球分化を制御し、一酸化炭素を介した免疫担当細胞間のシグナル架橋が存在することを示すことができた。また、COを治療分子とした新規治療法開発として、CO高含有溶解液作成が達成された。