Role of PAD4 for inflammatory diseases and neutrophil extracellular traps

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461494
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Nakashima Katsuhiko 国立研究開発法人国立がん研究センター, 研究所, 研究員 (90528035)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: シトルリン化

Outline of Final Research Achievements

Peptidylarginine deiminase 4 (PAD4) is a nuclear-localized citrullination enzyme and transcription regulator through citrullination of histone H3. It has been reported that PAD4 is essential for neutrophil extracellular traps (NETs) which is a event on bacterial infection and inflammation. In this study, we examined the role of PAD4 on acute lung injury (ALI) using PAD4-deficient mouse. The results showed expression of inflammatory cytokines, IL-6, TNF-alpha, MCP-1, and IL-1beta, were suppressed by PAD4-deficiency. Next, we assessed the role of PAD4 on macrophage differentiation of M1 cells, mouse myelocytic leukemia cells. Ectopic expression of PAD4 but not mutant PAD4 in M1 cells induced apoptosis during IL-6 treatment of M1 cells. In addition, c-myc expression on IL-6 treatment is suppressed by ectopic expression of PAD4 but not mutant PAD4. These results suggested that PAD4 plays important roles on inflammatory response, especially ALI.

Free Research Field

分子細胞生物学