Department of Clinical Laboratory, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, China.
Curr Microbiol. 2011 Oct;63(4):341-6. doi: 10.1007/s00284-011-9985-2. Epub 2011 Jul 22.
Chlamydiae are obligate intracellular bacteria that cause variety of human diseases. Chlamydia-infected host cells are profoundly resistant to apoptosis induced by many different apoptotic stimuli. The inhibition of apoptosis is thought to be an important immune escape mechanism allowing chlamydiae to productively complete their obligate intracellular growth cycle. Infection with chlamydiae can activate the Raf/MEK/ERK pathway. Because the survival pathway can modulate apoptosis, we used MEK-specific inhibitor U0126 and Raf-specific inhibitor GW5074 to examine the role of Raf/MEK/ERK pathway in chlamydial antiapoptotic activity. Apoptosis was induced by staurosporine (STS) and detected by morphology, DNA fragmentation, caspase-3 activation, and poly (ADP-ribose) polymerase cleavage. Inhibition of the pathway sensitized Chlamydia-infected cells to STS-mediated cell apoptosis. The data indicate that chlamydial antiapoptotic activity involves activation of the Raf/MEK/ERK survival pathway.
衣原体是一种专性细胞内细菌，可引起多种人类疾病。受衣原体感染的宿主细胞对多种不同凋亡刺激诱导的细胞凋亡具有很强的抗性。抑制细胞凋亡被认为是一种重要的免疫逃避机制，使衣原体能够有效地完成其专性细胞内生长周期。衣原体感染可激活 Raf/MEK/ERK 通路。由于存活途径可以调节细胞凋亡，我们使用 MEK 特异性抑制剂 U0126 和 Raf 特异性抑制剂 GW5074 来研究 Raf/MEK/ERK 通路在衣原体抗凋亡活性中的作用。用星形孢菌素（STS）诱导细胞凋亡，并通过形态学、DNA 片段化、caspase-3 激活和多聚（ADP-核糖）聚合酶切割检测。该途径的抑制使衣原体感染的细胞对 STS 介导的细胞凋亡敏感。数据表明，衣原体的抗凋亡活性涉及 Raf/MEK/ERK 存活途径的激活。
