粉尘螨变应原（Der f I）对DC2．4细胞的作用及其诱发哮喘机制的初步研究

Effect of Der f I on DC2.4, and the Mechanism of the Allergen Inducing Allergic Asthma

分别通过对DC2．4细胞白介素-12（IL-12）和IL-10的ELISA检测，蛋白酶激活受体（PAR-2）的基因表达和丝裂原活化蛋白酶（MAPK）p44／42的磷酸化来观察Der f I对DC2．4细胞的作用及其诱发哮喘机制的初步研究。Der f I作用于DC2．4细胞的结果显示，Der f I可促进DC2．4细胞IL-10的分泌（P〈0．01），抑制IL-12的分泌（P〈0．05），但信号通路抑制剂U0126可以逆转细胞因子的分泌模式；促进磷酸化p44／42MAPK的表达（尤其是促进p42的磷酸化）；抑制PAR．2受体的表达并呈时间依赖性。Th1／Th2失衡及Th2细胞功能亢进是过敏性哮喘的免疫基础，3312型免疫应答可能是哮喘发生的机制之一。本研究中由于Der f I作用于DC2．4细胞后抑制初始T细胞向Th1细胞分化而促使其向Th2细胞分化从而促使Th2型免疫应答，进而诱发过敏性哮喘，信号通路p44142MAPK的磷酸化加强和PAR-2受体表达的抑制也在诱发过敏性哮喘过程中起到促进作用。

To investigate the effect of I type allergen of Dermatophagoidesfarinae （Der f I ） on dendritic cells 2.4 （DC2.4） and the mechanism of the allergen inducing allergic asthma through determining the interleukin-12 （IL-12） and IL-10 of DC2.4 by ELISA, the expression of protease/proteinase-activated receptor （PAR-2） gene and the phosphorylation of mitogen-activated protein kinase （MAPK） p44/42, respectively. The results showed that Der f I enhanced DC2.4 to secrete IL-10 （ P 〈 0.01 ） and reduced DC2.4 to secrete IL-12 （ P 〈 0.05）, but U0126, a signal passageway inhibitor, may reverse the pattern of cytokines secretion, enhance the expression of phosphorylated p44/42 MAPK （especially enhance the phosphorylation of p42 ）, and reduce the expression of PAR-2 gene in a time-dependent manner. Th1/Th2 disequilibrium and Th2 hyperfunction were considered as the fundamental immunity of allergic asthma, and Th2 immune response may be one of the mechanisms inducing allergic asthma. In present study, the treatment of Der fI on DC2.4 reduced the differentiation of naive T cells to Thl cells, and enhanced to Th2 cells, accordingly activated the Th2 immune response, and then induced allergic asthma. The increased phosporylation of signal passageway p44/42 MAPK and the decreased expression of PAR-2 may play roles of inducing allergic asthma.