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

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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.