Cleavage of p65 Subunit of NF-κB by Orientia tsutsugamushi

Cleavage of p65 Subunit of NF-κB by Orientia tsutsugamushi
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恙虫病东方体对 NF-κB p65 亚基的裂解

DOI:
10.4167/jbv.2010.40.4.151
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发表时间:
2010
影响因子:
--
通讯作者:
Jae
Jae
中科院分区:
--
文献类型:
--
作者:
M. J. Kim;Sun;Se;Jae

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恙虫病东方体是恙虫病的病原体,是一种专性细胞内寄生虫,通常在宿主内皮细胞和巨噬细胞的细胞质中繁殖。巨噬细胞是抵抗细菌感染的第一道防线,NF-κB 在与细菌接触时被激活,导致炎症细胞因子的转录以控制细菌感染。在这项研究中,我们研究了恙虫病是否调节巨噬细胞中 NF-κB 的激活。我们检查了恙虫病感染后 NF-κB 蛋白的变化,根据 EMSA 和免疫印迹分析判断,NF-κB 的激活速度较慢。有趣的是,我们发现 p65 被切割,生成 45 kDa 的片段。此外,p65 片段仅由恙虫病毒力血清型菌株产生,表明这种切割可能与小鼠毒力有关。目前尚不清楚这是否是恙虫病蛋白或宿主细胞酶的直接结果。进一步探索恙虫病原虫调节 NF-κB 活性的机制,有助于更好地了解恙虫病原虫感染的分子发病机制。
Orientia tsutsugamushi, a causative agent of scrub typhus, is an obligate intracellular parasite and usually propagates in the cytoplasm of host endothelial cells and macrophages. Macrophages are the first defense line against bacterial infection and NF-κB is activated upon contact with bacteria, resulting in the transcription of inflammatory cytokine to control bacterial infection. In this study, we investigated whether O. tsutsugamushi modulates NF-κB activation in the macrophages. We examined the changes of NF-κB proteins upon infection with O. tsutsugamushi and found that NF-κB is activated at a slow rate as judged with EMSA and immunoblot analysis. Interestingly, we found that p65 was cleaved generating a 45 kDa fragment. In addition, fragment of p65 is generated only by the virulent serotype strain of O. tsutsugamushi, suggesting this cleavage may be associated with the mouse virulence. It is still unknown whether this is a direct result of O. tsutsugamushi proteins or enzymes of host cell. Further exploration of the mechanism that modulates NF-κB activity by O. tsutsugamushi could contribute to a better understanding of the molecular pathogenesis of O. tsutsugamushi infection.
DOI: --
发表时间: 1991
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
al-Ramadi,BK;Chen,YW;MeisslerJr,JJ;Eisenstein,TK
通讯作者: Eisenstein,TK