PKC-NF-kB信号传导系统对变应性鼻炎Th2细胞因子IL-4及IL-5表达的调控

目的：探讨PKC—NF—kB信号传导系统在调节变应性鼻炎（AR）T淋巴细胞的活化及IL-4、IL-5表达及其在发病过程中的作用。方法：24例急性发作期AR患者和24例健康成人为研究对象，分别从每位受试者的外周血中分离出T淋巴细胞并分成3组进行培养；第1组为空白对照（正常空白对照组及AR空白对照组）；第2组加入终浓度为20nmol／L的PKC激动剂12-肉豆蔻酰-13-乙酸佛波酯（PMA）（加PMA正常组及加PMAAR组）；第3组同时应用PKC激动剂PMA和终浓度为100μmol／L的NF-kB抑制剂二硫代氨基甲酸吡咯烷（PDTC）（加PMA和PDTC正常组及加PMA和PDTCAR组）。将培养的T淋巴细胞涂片，用免疫组织化学染色方法检测NF—kB的表达，用酶联免疫吸附（ELISA）法检测上清液中的IL-4及IL-5含量。结果：加PMAAR组T淋巴细胞NF-kB活化细胞百分比、培养上清液中的IL-4、IL-5与正常空白对照组及AR空白对照组比较，差异有统计学意义（均P〈0．01）；与加PMA正常组及加PMA和PDTC正常组T淋巴细胞比较，差异有统计学意义（均P〈0．01）；与加PMA和PDTCAR组T淋巴细胞比较，差异有统计学意义（P〈0．01）。同时，加PMA和PDTCAR组T淋巴细胞NF—kB活化细胞百分比、培养上清液中的IL-4、IL-5与加PMAAR组、AR空白对照组、正常空白对照、加入PMA正常组、加入PMA和PDTC正常组比较，差异有统计学意义（均P〈0．01）。T淋巴细胞NF—kB活化细胞的百分比与培养上清中IL-后使IL-4和IL-5的表达增加的生物信号能通过激活NF—kB来实现，T淋巴细胞的PKC—NF-kB信号传导系统可能是变应性鼻炎发病机制中的重要环节之一。

Regulation of the expression of interleukin-4 and interleukin-5 by the signal pathway of PKC-NF-kB in T lymphocyte of allergic rhinitis

OBJECTIVE: To explore the role of nuclear factor-kappaB(NF-kappaB) in the signal pathway of protein kinase C(PKC) regulating the expression of interleukin-4(IL-4) and interleukin-5(IL-5) by T lymphocyte in allergic rhinitis. METHOD: Twenty-four allergic rhinitis patients and 24 normal control persons participated in the study. T lymphocytes were isolated and purified from blood of each person and divided into 3 groups: cells of 1st group were control group(Normal control and AR control),cells of 2nd group were stimulated with phorbol 12-myristate 13-acetate (Normal PMA and AR PMA),cells of 3rd group were stimulated with PMA and pyrrolidine dithiocarbamate (Normal PMA/PDTC and AR PMA/PDTC). The expression of NF-kappaB were observed by immunocytochemical staining, 11-4 and IL-5 protein in supernatants were measured by ELISA. RESULT: The percentage of cells of active NF-kappaB, 11-4 and IL-5 protein in supernatants of allergic rhinitis T lymphocyte stimulated with PMA were significantly higher than those of allergic rhinitis T lymphocyte stimulated without PMA ( P < 0.01) and with PMA and PDTC( P < 0.01); than those of normal control T lymphocyte stimulated with PMA ( P < 0.01), with PMA and PDTC ( P < 0.01) and without PMA. The percentage of cells of active NF-kappaB, IL-4 and IL-5 protein in supernatants of allergic rhinitis T lymphocyte stimulated with PMA and PDTC were significantly lower than those of allergic rhinitis T lymphocyte stimulated with PMA (P < 0.01); but significantly higher than those of allergic rhinitis T lymphocyte stimulated without PMA and those of normal T lymphocyte stimulated. There were good positive correlation between the percentage of cells of active NF-kappaB and IL-4 and IL-5 protein in super-natants (r = 0.88,0.85, P < 0.01, respectively). CONCLUSION: The active PKC of allergic rhinitis T lymphocyte increasing the expression of IL-4 and IL-5 may be mediated by activating NF-kappaB, the activation of PKC-NF-kappaB signal pathway of T lymphocyte NF-kappaB may play an important role in the pathogenesis of allergic rhinitis.