重症继发性肺结核患者外周血单个核细胞c-Jun水平降低

Down-regulated expression of c-Jun in peripheral blood mononuclear cells of patients with severe secondary pulmonary tuberculosis

目的研究重症与轻症继发性肺结核患者c-Jun表达的差异,探讨其在重症继发性肺结核炎症反应和免疫损伤中的意义。方法用Affymetrix基因表达谱芯片筛选重症、轻症肺结核患者和正常健康者差异表达基因,并对差异基因进行生物信息学分析;用实时定量PCR(qRT-PCR)测定重症、轻症肺结核患者和健康者c-Jun相对水平;ELISA测定c-Jun在重症、轻症肺结核患者和健康者外周血单个核细胞(PBMC)中的蛋白水平。结果芯片筛选发现重症与轻症继发性肺结核患者存在大量差异表达基因,参与较多免疫反应和炎症反应通路,其中c-Jun表达下调2.27倍,参与61个信号通路;qRT-PCR结果显示,相比轻症继发性肺结核患者,c-Jun在重症继发性肺结核患者水平显著下调;ELISA检测也证实c-Jun表达在重症继发性肺结核患者有下调趋势,与芯片结果相符。结论重症与轻症继发性肺结核患者相比,c-Jun表达下调,c-Jun参与广泛的免疫反应和炎症反应通路,其下调与重症患者的免疫损伤有相关性。

[Abstract] Objective To compare the expression of c-Jun in severe versus mild secondary pulmonary tuberculosis （TB） and understand the relationship of the c-Jun expression with the inflammation and immune injury of severe secondary TB patients. Methods Differentially expressed genes were screened in patients with severe TB, the ones with mild TB and healthy controls using Affymetrix human gene expression chips. Bioinformatic analysis was performed on the results of the gene chip screening. The relative transcript level of c-Jun was detected by real-time quantitative PCR （qRT-PCR）. The protein expression of c-Jun in peripheral blood mononuclear cells was detected by ELISA. Results Patients with severe pulmonary TB exibited a large number of differentially expressed genes compared with healthy controls and patients with mild secondary TB, and these differential expressed genes involved complicated pathways of immue response and inflammation. C-Jun was down-regulated 2.27 times in the patients with severe secondary TB compared with the ones with mild TB, and it is involved in 61 pathways. The qRT-PCR verified that c-Jun was down-regulated significantly in the patients with severe secondary TB compared with the mild ones. ELISA confirmed the trend of down-regulation of c-Jun in the patients with severe secondary TB. The results of qRT-PCR and ELISA were consistent with gene chip analysis. Conclusion C-Jun was down-regulated in the patients with severe secondary TB compared with the patients with mild TB, and it is involved in many pathways of immue response and inflammation. Its down-regulation might be related to the immune injury of severe secondary TB.