Histone-like DNA binding protein of Streptococcus intermedius induces the expression of pro-inflammatory cytokines in human monocytes via activation of ERK1/2 and JNK pathways
Histone-like DNA binding protein of Streptococcus intermedius induces the expression of pro-inflammatory cytokines in human monocytes via activation of ERK1/2 and JNK pathways
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DOI：
10.1111/j.1462-5822.2007.01040.x
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发表时间：
2008-01-01
影响因子：
3.4
通讯作者：
Miyake, Yoichiro
中科院分区：
文献类型：
--
作者：
Liu, Dali;Yumoto, Hiromichi;Miyake, Yoichiro
中间链球菌是一种与主要器官（如脑和肝）的严重深层化脓性感染相关的寄生虫。组蛋白样DNA结合蛋白（HLP）是一种参与多种细菌细胞过程的辅助结构蛋白。本研究探讨了重组人链球菌HLP诱导THP-1细胞产生促炎细胞因子的机制。intermedius（r Si-HLP）。rSi-HLP刺激诱导的促炎细胞因子（IL-8、IL-1 β和TNF-α）的产生以时间和剂量依赖性方式发生。与DNA结合的热稳定活性相反，rSi-HLP的诱导活性是热不稳定的。在随后的研究中，rSi-HLP与脂磷壁酸、合成的Toll样受体2激动剂Pam 3CSK 4和胞质核苷酸结合寡聚化结构域2受体激动剂胞壁酰二肽协同作用。Western blot和特异性抑制剂阻断实验表明，rSi-HLP刺激可激活细胞外信号调节激酶1/2（extracellularsignal-regulatedkinase 1/2，ERK 1/2）和c-Jun N-末端激酶（c-Jun N-terminalkinase，JNK）。除了通过DNA结合在细菌生长中的生理作用外，这些结果表明Si-HLP可以通过ERK 1/2和JNK信号通路触发诱导促炎反应的级联反应，并表明细菌HLP可能有助于细菌感染期间宿主先天免疫的激活。
Streptococcus intermedius is a commensal associated with serious, deep-seated purulent infections in major organs, such as the brain and liver. Histone-like DNA binding protein (HLP) is an accessory architectural protein in a variety of bacterial cellular processes. In this study, we investigated the mechanisms of pro-inflammatory cytokine inductions in THP-1 cells by stimulation with recombinant HLP of S. intermedius (r Si-HLP). r Si-HLP stimulation-induced production of pro-inflammatory cytokines (IL-8, IL-1 beta and TNF-alpha) occurred in a time- and dose-dependent manner. In contrast with the heat-stable activity of DNA binding, the induction activity of rSi-HLP was heat-unstable. In subsequent studies, rSi-HLP acted cooperatively with lipoteichoic acid, the synthetic Toll-like receptor 2 agonist, Pam3CSK4, and the cytosolic nucleotide binding oligomerization domain 2 receptor agonist, muramyldipeptide. Furthermore, Western blot and blocking assays with specific inhibitors showed that rSi-HLP stimulation induced the activation of cell signal transduction pathways, extracellularsignal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). In addition to its physiological role in bacterial growth through DNA binding, these results indicate that Si-HLP can trigger a cascade of events that induce pro-inflammatory responses via ERK1/2 and JNK signal pathways, and suggest that bacterial HLP may contribute to the activation of host innate immunity during bacterial infection.