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目的:探究PE_PGRS60蛋白在结核分枝杆菌感染致病中的潜在作用机制。方法:用克隆并纯化的PE_PGRS60蛋白刺激RAW264.7小鼠巨噬细胞，qRT-PCR和Western blot检测环氧合酶2(cyclooxygenase 2, COX2) mRNA和蛋白质表达。筛选可能调控COX2表达的信号通路，并用ELISA检测PE_PGRS60诱导的炎性细胞因子表达，乳酸脱氢酶试验和碘化丙啶(PI)染色，流式细胞术观察细胞死亡情况。Western blot检测活动性肺结核患者的外周血单个核细胞(PBMC)中COX2表达情况。结果:克隆纯化的结核分枝杆菌PE_PGRS60蛋白促进RAW264.7细胞中COX2的显著表达，并活化了MAPK家族的3个主要成员即细胞外调节蛋白激酶(extracellular regulated protein kinase, ERK)、p38和c-Jun氨基末端激酶(c-Jun N-terminal kinase, JNK)，但只有JNK的抑制剂JNK-IN-7可阻断PE_PGRS60诱导的COX2上调。后续研究发现，COX2在活动性肺结核患者PBMC中的表达也升高。COX2抑制剂塞来昔布可有效阻断PE_PGRS60诱导的炎症因子IL-1β、TNF-α和IL-6表达，并促进巨噬细胞死亡。结论:PE_PGRS60可通过激活JNK/COX2信号轴，促进巨噬细胞释放炎症因子，在COX2的阻止下仍有部分巨噬细胞发生死亡。“,”Objective:To investigate the mechanism of PE_PGRS60 protein in the pathogenesis of n Mycobacterium tuberculosis infection.n Methods:The cloned and purified PE_PGRS60 protein from n Mycobacterium tuberculosis was used to stimulate RAW264.7 cells. The expression of cyclooxygenase 2(COX2) mRNA and protein was detected by qRT-PCR and Western blot, respectively. The signal pathways that may regulate the expression of COX2 were screened, and the expression of inflammatory cytokines induced by PE_PGRS60 was detected by ELISA. The level of cell death was measured by lactate dehydrogenase(LDH) release test and flow cytometry PI staining. Western blot was used to detect the expression of COX2 in Peripheral blood mononuclear cell(PBMC) from active tuberculosis patients.n Results:PE_PGRS60 protein was found to promote the expression of COX2 in RAW264.7 cells and activate the three major members of the mitogen-activated protein kinase(MAPK) family: extracellular regulated protein kinase(ERK), p38 and c-Jun N-terminal kinase(JNK). Interestingly, only JNK-IN-7, the inhibitor of JNK was observed to suppress the up-regulation expression of COX2 induced by PE_PGRS60. This up-regulated expression of COX2 was also found in PBMCs from active tuberculosis patients. The COX2 inhibitor celecoxib can effectively block the expression of the inflammatory factors IL-1β, TNF-α and IL-6 induced by PE_PGRS60 and promote macrophage death.Conclusions:PE_PGRS60 can promote macrophages to release inflammatory factors by activating JNK/COX2 signal axis. Some macrophages still die under the protection of COX2.