Establishment of gene therapy for the regulation of IgE and Chemokine production in patients with nasal allergy

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Nasal fibroblasts stimulated by cytokines released the chemokine and play a key role in pathogenesis of allergic rhinitis.Syk proteins were expressed in human nasal fibroblasts, but the expression level varied.There were positive correlation between the level of Syk expression and RANTES production by LPS.Over expression of wild-type Syk by gene transfer enhanced RANTES production.Administration of Syk-antisense inhibited RANTES production. JNK1 and p38 MAP kinase are important for RANTES production. Four types of dominant positive mutant Ras were made and transfected into nasal fibroblast. When PI3kinase pathway was activated by Ras mutant, nasal fibroblast produced the largest amount of RANTES.Double strand RNA(dsRNA) also induced RANTES production by nasal fibroblast.The addition of IFNg enhanced RANTES production by dsRNA, while IL4 had no effect to enhance RANTES production.Eotaxin was not induced by dsRNA. However, IL-4 and deRNA had syngergistic effect to induce Eotaxin production by nasal fibroblst. Nasal fibroblast expressed CCR3, which is a regand to RANTES and Eotaxin.The treatment of RANTES increased CCR 3 expression on nasal fibroblast and induced cell growth in the manner of autocrine.CD45 molecules regulated IgE class switching on B cells via JNK pathway.The new method to quantify IgE class swithing was established.Human IgG-IgE chimeric protein inhibit IgE class switch recombination by co-aggregating B cell CD32 and CD23.This protein directly inhibited germline transcription, subsequent class switching to and IgE production.