Identification of novel zinc-responsive protein and clarification of significance in colorectal cancer prevention

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K16281
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Eating habits
• Research Institution: Ishikawa Prefectural University
• Principal Investigator: HIGASHIMURA YASUKI 石川県立大学, 生物資源環境学部, 助教 (70628924)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 亜鉛 / 大腸炎 / マクロファージ / リンパ球 / Th17

Outline of Final Research Achievements

Hypozincemia regarded as a risk for colon cancer and colitis. However, the precise mechanisms involved in zinc deficiency of the intestinal inflammation remains unclear. This study demonstrates that zinc deficiency resulting from using a zinc chelator administration aggravates colonic inflammation through the activation of type 17 helper T (Th17) cells in mice. Flow cytometric analysis revealed that zinc deficiency significantly increases the proportion of pro-inflammatory (M1) macrophages in inflamed colon. A zinc chelator up-regulates IL-23p19 expression, which is deeply associated with Th17 development, in mouse bone marrow-derived macrophages (BMDMs). Furthermore, the nuclear accumulation of interferon-regulatory factor 5 is critically involved in IL-23p19 induction in zinc-deficient BMDMs. Thus, zinc deficiency aggravates colonic inflammation through activation of the IL-23/Th17 axis, and the activation is controlled by subcellular distribution of interferon-regulatory factor 5.

Free Research Field

食品生化学