Actinobacillus actinomycetemcomitans Y4 capsular polysaccharide induces IL-1β mRNA expression through the JNK pathway in differentiated THP-1 cells
Actinobacillus actinomycetemcomitans Y4 capsular polysaccharide induces IL-1β mRNA expression through the JNK pathway in differentiated THP-1 cells
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DOI：
10.1111/j.1365-2249.2005.02836.x
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发表时间：
2005-08-01
影响因子：
4.6
通讯作者：
Noguchi, T
中科院分区：
文献类型：
--
作者：
Iwata, T;Mitani, A;Noguchi, T
如先前的研究所报道的，来自伴放线放线杆菌Y 4（Y 4 CP）的荚膜多糖诱导小鼠器官培养系统中的骨吸收和小鼠骨髓培养中的破骨细胞形成。我们还发现Y 4 CP抑制人牙龈成纤维细胞（HGF）释放白细胞介素（IL）-6和IL-8。因此，Y 4 CP在局部组织中诱导各种反应并导致几种细胞因子的分泌。然而，Y 4 CP对人单核细胞/巨噬细胞的影响仍不清楚。在这项研究中，THP-1细胞，这是一个人单核细胞系，与Y 4 CP刺激，我们测量了炎症细胞因子和信号转导通路的基因表达。IL-1 β和肿瘤坏死因子（TNF）-α mRNA诱导Y 4 CP处理的THP-1细胞。IL-1 β mRNA表达随Y 4 CP剂量增加而增加，并呈时间依赖性。通过实时PCR分析，Y 4 CP（100 μ g/ml）诱导的IL-1 β mRNA表达比对照组高约7- 10倍。细胞外信号调节激酶（ERK）特异性抑制剂PD 98059和p38激酶特异性抑制剂SB 203580均不能抑制Y 4 CP诱导的IL-1 β表达。而JNK Inhibitor II（c-Jun N-末端激酶（JNK）的特异性抑制剂）以浓度依赖性方式抑制Y 4 CP诱导的IL-1 β mRNA表达。这些结果表明，Y 4 CP介导的JNK通路在IL-1 β mRNA的调节中起重要作用。因此，在巨噬细胞的抗菌作用中，Y 4 CP转导的IL-1 β诱导信号可能提供牙周炎的治疗策略。
Capsular polysaccharide from Actinobacillus actinomycetemcomitans Y4 (Y4 CP) induces bone resorption in a mouse organ culture system and osteoclast formation in mouse bone marrow cultures, as reported in previous studies. We also found that Y4 CP inhibits the release of interleukin (IL)-6 and IL-8 from human gingival fibroblast (HGF). Thus Y4 CP induces various responses in localized tissue and leads to the secretion of several cytokines. However, the effects of Y4 CP on human monocytes/macrophages are still unclear. In this study, THP-1 cells, which are a human monocytic cell line, were stimulated with Y4 CP, and we measured gene expression in inflammatory cytokine and signal transduction pathways. IL-1 beta and tumour necrosis factor (TNF)-alpha mRNA were induced from Y4 CP-treated THP-1 cells. IL-1 beta mRNA expression was increased according to the dose of Y4 CP, and in a time-dependent manner. IL-1 beta mRNA expression induced by Y4 CP (100 mu g/ml) was approximately 7- to 10-fold greater than that in the control by real-time PCR analysis. Furthermore, neither PD98059, a specific inhibitor of extracellular signal-regulated kinase nor SB203580, a specific inhibitor of p38 kinase prevented the IL-1 beta expression induced by Y4 CP. However, JNK Inhibitor II, a specific inhibitor of c-Jun N-terminal kinase (JNK) prevented the IL-1 beta mRNA expression induced by Y4 CP in a concentration-dependent manner. These results indicate that Y4 CP-mediated JNK pathways play an important role in the regulation of IL-1 beta mRNA. Therefore, Y4 CP-transduced signals for IL-1 beta induction in the antibacterial action of macrophages may provide a therapeutic strategy for periodontitis.