Myeloperoxidase negatively regulates the expression of proinflammatory cytokines and chemokines by mouse neutrophils

2016 Fiscal Year Final Research Report

• Project/Area Number: 26450446
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Integrative animal science
• Research Institution: Yokohama City University
• Principal Investigator: Aratani Yasuaki 横浜市立大学, 生命ナノシステム科学研究科(八景キャンパス), 教授 (30192470)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 免疫 / 好中球 / ミエロペルオキシダーゼ / 活性酸素 / 炎症

Outline of Final Research Achievements

Myeloperoxidase (MPO) and NOX2, major constituents of neutrophils that generate reactive oxygen species (ROS), contribute to microbial killing. This study aimed to evaluate the effect of MPO deficiency and NOX2 deficiency on lung inflammation induced by zymosan and nonviable Candida. Mice deficient in these enzymes showed more severe neutrophilic pneumonia than wild-type mice, which exhibited higher lung concentrations of proinflammatory cytokines chemokines. In vitro, production of these inflammatory mediators from neutrophils was enhanced in the mutant neutrophils, concomitant with upregulation of ERK/NF-κB pathway. We also found that upregulation of the CD11b/FAK/ERK pathway due to absence of MPO enhances the phagocytic activity of neutrophils. These results suggest that lack of ROS production results in the production of higher levels of proinflammatory mediators. Thus, loss of ROS production by neutrophils causes significant abnormalities in both host defense and inflammation.

Free Research Field

免疫生物学