CPSIT_p7通过激活JNK/ERK信号通路诱导宿主细胞炎症

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目的初步探讨鹦鹉热嗜衣原体蛋白CPSIT_p7对宿主细胞炎症反应的调节作用及其分子机制。方法佛波酯(PMA)处理THP-1细胞过夜,诱导其分化为贴壁的巨噬细胞,之后用CPSIT_p7蛋白刺激贴壁细胞,或先用30μmol/L ERK抑制剂PD98059、JNK抑制剂SP600125和p38抑制剂SB202190分别预处理贴壁细胞,再用CPSIT_p7蛋白处理贴壁细胞;Western blot检测ERK、JNK和p38磷酸化水平,ELISA检测各种炎症因子的表达水平。结果 0~10μg/ml CPSIT_p7蛋白刺激PMA诱导的THP-1细胞24 h后,随着CPSIT_p7质量浓度升高,IL-6、IL-1β、IL-8及TNF-α的含量呈剂量依赖性增加;10μg/ml的CPSIT_p7处理细胞0、6、12、24和36 h,在24 h时IL-6、IL-8及IL-1β表达水平达到高峰,而TNF-α在12 h就达到高峰;CPSIT_p7蛋白处理细胞后其ERK和JNK磷酸化水平显著升高,p38磷酸化水平改变不明显;JNK和ERK抑制剂能明显降低CPSIT_p7蛋白诱导的IL-6、IL-1β、IL-8及TNF-α表达。结论 CPSIT_p7通过JNK/MAPKs和ERK/MAPKs信号传导途径诱导THP-1产生IL-1β、IL-6、IL-8及TNF-α炎症因子,与p38/MAPKs信号传导通路无关。 OBJECTIVE: To investigate the regulatory effect of CPSIT_p7, a Parrot, Chlamydophila parvovirus, on the host cell inflammatory response and its molecular mechanism. Methods THP-1 cells were treated with phorbol ester (PMA) overnight and induced to differentiate into adherent macrophages. The cells were stimulated with CPSIT_p7 protein or treated with 30 μmol / L ERK inhibitor PD98059, JNK inhibitor SP600125 and Adherent cells were pretreated with SB202190, a p38 inhibitor, and treated with CPSIT_p7 protein. The phosphorylation levels of ERK, JNK and p38 were detected by Western blot and the expression of various inflammatory cytokines were detected by ELISA. Results After stimulated by PPS-induced THP-1 cells with 0-10 μg / ml CPSIT_p7 for 24 h, the concentrations of CPSIT_p7 increased the concentrations of IL-6, IL-1β, IL-8 and TNF-α in a dose-dependent manner The expression of IL-6, IL-8 and IL-1β reached a peak at 24 h after treatment with 10 μg / ml CPSIT_p7 at 0, 6, 12, 24 and 36 h, The phosphorylation levels of ERK and JNK were significantly increased and the phosphorylation level of p38 was not significantly changed after treatment with CPSIT_p7 protein. JNK and ERK inhibitors could significantly reduce the levels of IL-6, IL-1β, IL-8 and TNF- α expression. Conclusion CPSIT_p7 can induce THP-1 to produce IL-1β, IL-6, IL-8 and TNF-α inflammatory factors through JNK / MAPKs and ERK / MAPKs signal pathways, and has nothing to do with p38 / MAPKs signal transduction pathway.
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