| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| 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.
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