Molecular mechanism of cold induced anti-inflammation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06858
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Jichi Medical University
• Principal Investigator: SUGIMOTO Hiroki 自治医科大学, 医学部, 助教 (70515866)
• Co-Investigator(Kenkyū-buntansha): 武田 憲彦 自治医科大学, 医学部, 非常勤講師 (40422307)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: マウス / 炎症 / 温度 / 低温 / マクロファージ

Outline of Final Research Achievements

This study aimed to elucidate the molecular mechanism underlying the temperature-dependent anti-inflammation effect, characterized by an increase in the expression of Arginase1, using the IL4-STAT6-Arg1 signaling pathway in macrophages as a model. While focusing on the E3 ligase Cbl-b as a candidate regulator of this signaling pathway, knockdown of Cbl-b by siRNA did not induce an increase in Arginase1 expression. Conversely, the expression of Arginase1 was significantly suppressed by a Ca2+ chelator. Therefore, a novel role of Ca2+ signaling as a regulator of the IL4-STAT6-Arg1 signaling pathway was identified. This pathway plays a significant role in the temperature-dependent anti-inflammation effect.

Free Research Field

細胞

Academic Significance and Societal Importance of the Research Achievements

本研究では、マクロファージにおけるIL4-STAT6-Arg1シグナル系をモデルとした低温依存的な炎症終息経路の解析を行い、新たにCa2+シグナルリングが関与することを明らかにした。今後、このCa2+シグナリング経路に注目することで、低温シグナルが、炎症を終息させる機構の詳細を解明できると考えられる。低温依存的な炎症終息の機構の解明は、レイノー現象や肺高血圧症など外部環境温度によりその病態が影響を受ける様々な疾患に対する病態理解や新規治療アプローチの創出への貢献が期待できる。