Investigation of role and mechanism of pyroptosis in acute lung injury

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16199
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Jichi Medical University
• Principal Investigator: Mizushina Yoshiko 自治医科大学, 医学部, 講師 (70458321)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 炎症 / 細胞死 / 細胞・組織 / 肺疾患 / 免疫学

Outline of Final Research Achievements

We investigated the role of pyroptosis in acute lung injury (ALI) using the nanosilica-induced ALI model. Although nanosilica induced GSDME processing by activating caspase-3 in pulmonary epithelial cell line A549 cells, cell death was not ameliorated in caspase-3-deficient A549 cells. Therefore, we focused on necroptosis, another type of regulated cell death. RIPK1 inhibitor didn’t ameliorate lung injury in nanosilica-induced mouse ALI model, although the RIP3 inhibitor (necroptosis inhibition) ameliorated nanosilica-induced A549 cell death. These results suggest that more than one cell death contributes to nanosilica-induced ALI.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

ALIの病態に炎症が関与することが示されているが、その詳細は不明で、有効な治療方法も確立されていない。制御された細胞死（RCD）は様々な病態における炎症の起点となりうることがわかってきているが、ALIにおけるRCDの関与については不明な点が多い。本研究ではALIにおける肺胞上皮細胞におけるPyroptosisの関与やプロセシング機構を明らかにし、さらにPyroptosis以外のRCDの関与についても解析を進めており、本研究成果はALIの病態解明や新たな治療戦略の開発につながるのみならず、無菌性炎症が関与する様々な疾患の病態解明に役立つ可能性がある。