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。Poly(I：C)可促进人鼻成纤维细胞分泌RANTES和IL-8。但不分泌嗜酸性粒细胞趋化因子、IL-1β、肿瘤坏死因子-α、干扰素α、干扰素γ和IL-12。JNK抑制剂SP600125和PI3-激酶抑制剂LY294002显著阻断PolyI：C诱导的RANTES和IL-8的释放，而p38 MAP激酶抑制剂SB203580抑制PolyI：C诱导的IL-8的分泌，但不抑制RANTES的分泌。IL-4产生的嗜酸性粒细胞趋化因子与鼻腔成纤维细胞中SOCS5的表达通过PI3-激酶途径相关。用聚(I：C)诱导B淋巴细胞刺激蛋白(BLyS)。BLyS诱导IgE类转换。BlyS的分泌与Rho、Syk、Vav、c-Src、TRAF6、p-选择素有关，浆细胞样树突状细胞通过连接TLR9未甲基化的CpG基序产生大量干扰素α。CpG DNA增强了核因子-KB亚基p65/p50的活性，与p38MAPK协同上调IRF-7、CXCL10和CCL3的表达，这种作用不依赖于I型干扰素信号。I型干扰素以非依赖的方式诱导IRF-7表达，但不诱导干扰素α的表达。CpGDNA可使I型干扰素诱导的pDC在NF-KB/p38MAPK抑制剂存在的情况下表达干扰素α，氯喹可阻断这一作用。有了CpG DNA，IRF-7，无论是结构性的还是新表达的，都转移到了不依赖于NF-KB/p38MAPK的细胞核。日本对季节性变应性鼻炎进行了林下免疫治疗(Sit)。我们发现有8种蛋白质在切开后血清中升高。蛋白质的含量与临床转归相关。在48,000个转录本中，接受SIT治疗的患者PBMC中32个基因的表达增加。

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.