Yun Ji-Hyun, Koo Jung-Eun, Koh Young-Sang
Department of Microbiology, School of Medicine, BK21 Program, and Institute of Medical Science, Cheju National University, Jeju 690-756, Republic of Korea.
Microbiol Immunol. 2009 Jun;53(6):349-55. doi: 10.1111/j.1348-0421.2009.00127.x.
Orientia tsutsugamushi, an obligatory intracellular bacterium, is the causative agent of scrub typhus. Here the role of MAPK in TNF-alpha production in macrophages after infection with O. tsutsugamushi has been investigated. ERK1/2, JNK, and p38 MAPK became phosphorylated in Orientia-stimulated macrophages. Selective inhibitors of MAPK cascades could all significantly reduce Orientia-stimulated TNF-alpha production. Orientia-stimulated TNF-alpha production via p38 and JNK pathways was regulated by a post-transcriptional mechanism, whereas the ERK pathway mainly controlled the transcriptional step of TNF-alpha gene expression during infection. In conclusion, our data indicate that MAPK signaling is required to induce maximal TNF-alpha production in macrophages during Orientia infection.
恙虫病东方体是一种专性细胞内细菌，是恙虫病的病原体。在此，研究了丝裂原活化蛋白激酶（MAPK）在恙虫病东方体感染后巨噬细胞中肿瘤坏死因子-α（TNF-α）产生过程中的作用。在经恙虫病东方体刺激的巨噬细胞中，细胞外信号调节激酶1/2（ERK1/2）、应激活化蛋白激酶（JNK）和p38丝裂原活化蛋白激酶发生了磷酸化。MAPK级联反应的选择性抑制剂均可显著降低经恙虫病东方体刺激的TNF-α产生。经恙虫病东方体刺激通过p38和JNK途径产生的TNF-α受转录后机制调控，而ERK途径在感染期间主要控制TNF-α基因表达的转录步骤。总之，我们的数据表明，在恙虫病东方体感染期间，MAPK信号传导是诱导巨噬细胞中最大程度TNF-α产生所必需的。
