| Co-Investigator(Kenkyū-buntansha) |
YAMADA Takechiyo University of Fukui, Hospital, Associate Professor (70283182)
FUJIBAYASHI Yasuhisa University of Fukui, Biomedical Imaging Research Center, Professor (50165411)
SUGIHARA Shinji University of Fukui, Graduate School of Engineering, Assistant Professor (70377472)
KIMURA Yuichi University of Fukui, Faculty of Medical Sciences, Assistant Professor (50281035)
杉本 千鶴 福井大学, 医学部附属病院, 助手 (80283183)
大澤 陽子 福井大学, 医学部附属病院, 医員 (40397253)
高橋 昇 福井大学, 医学部, 助手 (80293421)
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| Budget Amount *help |
¥16,530,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥930,000)
Fiscal Year 2007: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2006: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥9,300,000 (Direct Cost: ¥9,300,000)
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| Research Abstract |
We proposed that fibroblasts are not passive players in the immune system. Incubation with poly(I:C) enhanced the secretion of RANTES and IL-8 from human nasal fibroblasts. However, eotaxin, IL-1β, TNF-α, IFNα, IFNγ and IL-12 were not secreted. The JNK inhibitor SP600125 and PI3-kinase inhibitor LY294002 significantly blocked the poly(I:C)-induced release RANTES and IL-8, whereas the p38 MAP kinase inhibitor SB203580 suppressed poly(I:C)-induced secretion of IL-8, but not RANTES. Eotaxin production by IL-4 is correlated with expression of SOCS5 in nasal fibroblast via PI3-kinase pathway. B lymphocyte stimulator protein (BLyS) was induced by poly(I:C). BLyS induced IgE class switching. Secretion of BLyS is associated with Rho, Syk, Vav, c-Src, TRAF6, p-Selectin.
Plasmacytoid dendritic cells (pDC) produce a large amount of IFNα, through the ligation of TLR9 unmethylated CpG motifs. CpG DNA enhanced the NF-KB subunits p65/p50 activity, which collaborated with p38 MAPK to up-regulate the expression of IRF-7, CXCL10 and CCL3 in a manner independent of type I IFN signaling. Type I IFN induced the expression of IRF-7, but not of IFNα, in a NF-KB -independent way. CpG DNA enabled the type I IFN-treated pDC to express IFNα in the presence of NF-KB/p38 MAPK inhibitor, and chloroquine abrogated this effect. With CpG DNA, IRF-7, both constitutively and newly expressed, moved to the nuclei independent of NF-KB/p38 MAPK.
Sublingeal immunotherapy (SLIT) was performed for seasonal allergic rhinitis in Japan. We found 8 proteins that increased in serum after SLIT. The amount of proteins is correlated with clinical outcome. Of 48,000 transcripts, 32-gene expression is increased in PBMC in patients received with SLIT.
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