Hu Chang-Hua, Xie Jian-Ping, Li Yao, Yue Jun, Xu Yong-Zhong, Wang Hong-Hai
Institute of Modern Biopharmaceuticals, School of Life Science, Southwest China Normal University, Chongqing 400715, China.
Yi Chuan Xue Bao. 2004 Mar;31(3):231-5.
Tuberculosis(TB) remains one of the major problems in global health. Macrophage (MPhi) apoptosis, induced by Mycobacterium tuberculosis (Mtb), is a cornerstone of effective innate microbial defense mechanism. Elucidation of the complex apoptosis-related gene expression may facilitate understanding the mechanism and regulation of macrophage apoptosis in response to Mtb, and contribute to developing novel measures to counter TB. DNA microarray containing 19,200 gene or gene fragments was used to compare the macrophage cell line U937 gene expression response to the clinical and laboratory Mtb infection. Northern blotting and RT-PCR were used to confirm the microarray results. Mtb H37Rv infection were found to downregulate the bcl-2, vitamin D receptor, interferon regulatory factor 3, cytochrome c oxidase, gene expression by 2-, 3-, 3-, 2.5-fold, respectively, while the clinical strain infection leads to upregulate the SOD2, SOD3, serine protease, toll-like receptor 2, signal transducer and activator (STAT1), hypoxia-inducible factor 22, 2.9-, 2.5-, 2.5-, 2.2-, 2.4-, 5.9-fold respectively. The findings suggest that the clinical strain infection tends to override the macrophage apoptosis by which the host attempt to limit the growth of the invader. The research on the complex factors network involved in the interaction will benefit the vaccine and novel drug target development.
结核病(TB)仍是全球卫生领域的主要问题之一。结核分枝杆菌(Mtb)诱导的巨噬细胞(MPhi)凋亡是有效的先天性微生物防御机制的基石。阐明复杂的凋亡相关基因表达可能有助于理解巨噬细胞对Mtb反应的凋亡机制和调控,并有助于开发对抗结核病的新措施。使用包含19200个基因或基因片段的DNA微阵列来比较巨噬细胞系U937对临床和实验室Mtb感染的基因表达反应。采用Northern印迹法和RT-PCR来证实微阵列结果。发现Mtb H37Rv感染分别使bcl-2、维生素D受体、干扰素调节因子3、细胞色素c氧化酶的基因表达下调2倍、3倍、3倍、2.5倍,而临床菌株感染则导致超氧化物歧化酶2(SOD2)、超氧化物歧化酶3(SOD3)、丝氨酸蛋白酶、Toll样受体2、信号转导子和激活子(STAT1)、缺氧诱导因子2的基因表达分别上调2.9倍、2.5倍、2.5倍、2.2倍、2.4倍、5.9倍。这些发现表明,临床菌株感染倾向于抑制巨噬细胞凋亡,而宿主试图通过这种凋亡来限制入侵者的生长。对参与这种相互作用的复杂因素网络的研究将有利于疫苗和新型药物靶点的开发。