Tachibana Masato, Watanabe Kenta, Yamasaki Yuki, Suzuki Hiroshi, Watarai Masahisa
Department of Applied Veterinary Science, Obihiro University of Agriculture and Veterinary Medicine, Obihiro-shi, Hokkaido 080-8555, Japan.
Microb Pathog. 2008 Aug;45(2):105-9. doi: 10.1016/j.micpath.2008.04.002. Epub 2008 Apr 16.
Brucella abortus is a facultative intracellular pathogen that can survive inside macrophages and trophoblast giant (TG) cells, and the causative agent of brucellosis. In the present study, we found that expression of heme oxygenase-1 (HO-1) in TG cells is correlated with abortion induced by B. abortus infection in pregnant mice. Expression of HO-1 in the placenta was decreased by B. abortus infection and treatment with cobalt-protoporphyrin (Co-PP), which is known to up-regulate HO-1 expression, inhibited abortion due to the bacterial infection. In TG cells, treatment with Co-PP was shown to up-regulate HO-1, whereas its expression was decreased by B. abortus infection. Such down-regulation of HO-1 in the TG cells was enhanced by IFN-gamma treatment. HO-1 down-regulation in TG cells due to knockdown or IFN-gamma treatment served to induce cell death caused by B. abortus infection. These results suggest that down-regulation of HO-1 in TG cells due to B. abortus infection is an important event in infectious abortion.
牛布鲁氏菌是一种兼性胞内病原体，可在巨噬细胞和滋养层巨细胞（TG细胞）内存活，是布鲁氏菌病的病原体。在本研究中，我们发现TG细胞中血红素加氧酶-1（HO-1）的表达与怀孕小鼠感染牛布鲁氏菌诱导的流产相关。牛布鲁氏菌感染可降低胎盘HO-1的表达，而用已知可上调HO-1表达的钴原卟啉（Co-PP）处理可抑制细菌感染导致的流产。在TG细胞中，Co-PP处理可上调HO-1表达，而牛布鲁氏菌感染则使其表达降低。γ-干扰素处理可增强TG细胞中HO-1的这种下调。由于敲低或γ-干扰素处理导致TG细胞中HO-1下调会引发牛布鲁氏菌感染所致的细胞死亡。这些结果表明，牛布鲁氏菌感染导致TG细胞中HO-1下调是感染性流产中的一个重要事件。
