Does coffee polyphenol inhibit the level of MIF and the development of inflammatory carcinogenesis.

• Project/Area Number: 18K05500
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38050:Food sciences-related
• Research Institution: Hokkaido University
• Principal Investigator: Ohkawara Tatsuya 北海道大学, 薬学研究院, 研究員 (00374257)
• Co-Investigator(Kenkyū-buntansha): 武田 宏司 北海道大学, 薬学研究院, 特任教授 (60261294)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: マクロファージ遊走阻止因子 / コーヒーポリフェノール / クロロゲン酸 / 炎症 / 大腸腫瘍 / 炎症性発癌 / 大腸炎 / 大腸癌

Outline of Final Research Achievements

The role of macrophage migration inhibitory factor (MIF) in inflammatory colorectal carcinogenesis and the effects of coffee polyphenol components on the regulation of MIF expression were analyzed.We found that the expression of MIF was enhanced in colorectal tissue in colorectal cancer model. Especially, it was extremely high expression in colorectal tumor cells.MIF-deficient mice presented the reduction of colon tumors in this model compared with wild type mice.Moreover, there was a tendency to decrease oxidative stress and cyclooxygenase expression in the colon tissues of MIF-deficient mice compared with wild type mice. Chlorogenic acid also suppressed MIF secretion in murine macrophage cell-line.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は未だその役割が解明途上のマクロファージ遊走阻止因子の新たな機能解析が明らかになったこと、特に炎症・発癌機構での役割の機能解析が進んだことが学術的な意義である。マクロファージ遊走阻止因子は未だその活性や発現を制御するような臨床開発が進まず、その中で本研究によりコーヒー成分の一つがその候補となる可能性を示唆することができたのは社会的な意義を持つといえる。

Research Products

• [Journal Article] Protective effect of ISO-1 with inhibition of RIPK3 up-regulation and neutrophilic accumulation on acetaminophen-induced liver injury in mice (2021)
  • Author(s): Ohkawara Tatsuya、Okubo Naoto、Maehara Osamu、Nishihira Jun、Takeda Hiroshi
  • Journal Title: Toxicology Letters Volume: 339 Pages: 51-59
  • DOI: 10.1016/j.toxlet.2020.12.015
  • Peer Reviewed
• [Journal Article] The delivery of mRNA to colon inflammatory lesions by lipid-nano-particles containing environmentally-sensitive lipid-like materials with oleic acid scaffolds. (2018)
  • Author(s): Tanaka H, Watanabe A, Konishi M, Nakai Y, Yoshioka H, Ohkawara T, Takeda H, Harashima H, Akita H.
  • Journal Title: Heliyon Volume: 4 Issue: 12 Pages: e00959-e00959
  • DOI: 10.1016/j.heliyon.2018.e00959
  • Peer Reviewed / Open Access