| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
Recently we demonstrated that endoplasmic reticulum aminopeptidase 1 (ERAP1) was secreted from macrophages in response to LPS and IFN-γ, and it enhanced their phagocytic activity. In this study, we analyzed the mechanisms of ERAP1 secretion and phagocytosis activation by secreted ERAP1. TLR ligands such as exogenous lipopolysaccharide, lipoprotein and DNA induced secretion of the enzyme from the murine macrophage cell line RAW264.7 and murine peritoneal macrophages. These secretions were suppressed by deletion of either TNF-α or type 1 IFNR gene, suggesting that TNF-α and type I IFN expressed by TLR signaling are important for ERAP1 secretion. On the other hand, we found the exon 10 sequence of ERAP1 gene is crucial for ER-retantion and extracellular ERAP1 complexed with several cytokines showed more effective on phagocytosis than ERAP1 only. These results suggest that ERAP1 secretion is key event for classical activation of macrophages.
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