Analysis of allergic rhinitis by nano level and development of novel therapy

我们认为成纤维细胞在免疫系统中不是被动的参与者。与poly（I：C）孵育增强人鼻成纤维细胞分泌RANTES和IL-8。而Eotaxin、IL-1β、TNF-α、IFNα、IFNγ和IL-12均不分泌。JNK抑制剂SP 600125和PI 3激酶抑制剂LY 294002显著阻断poly（I：C）诱导的RANTES和IL-8的分泌，而p38 MAP激酶抑制剂SB 203580抑制poly（I：C）诱导的IL-8的分泌，但不抑制RANTES。IL-4产生的Eotaxin通过PI 3-激酶途径与鼻成纤维细胞中SOCS 5的表达相关。用poly（I：C）诱导产生B淋巴细胞刺激蛋白（BLyS）。BLyS诱导IgE类别转换。浆细胞样树突状细胞（Plasmacytoid dendritic cells，pDC）通过连接TLR 9非甲基化的CpG基序产生大量IFNα。CpG DNA增强NF-κ B亚基p65/p50的活性，其与p38 MAPK协同作用以独立于I型IFN信号的方式上调IRF-7、CXCL 10和CCL 3的表达。I型IFN以NF-κ B非依赖性方式诱导IRF-7的表达，但不诱导IFNα的表达。在NF-κ B/p38 MAPK抑制剂存在下，CpG DNA能使I型IFN处理的pDC表达IFNα，氯喹消除了这种作用。在CpG DNA的作用下，组成型和新表达的IRF-7不依赖于NF-κ B/p38 MAPK而移动到细胞核。我们发现SLIT后血清中有8种蛋白质增加。蛋白质的量与临床结果相关。在接受SLIT的患者中，在48，000个转录物中，32个基因的表达在PBMC中增加。

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.