Modulation of Wnt5a expression by periodontopathic bacteria.
Modulation of Wnt5a expression by periodontopathic bacteria.
复制标题
DOI：
10.1371/journal.pone.0034434
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Izumi Y
中科院分区：
文献类型：
--
作者：
Nanbara H;Wara-aswapati N;Nagasawa T;Yoshida Y;Yashiro R;Bando Y;Kobayashi H;Khongcharoensuk J;Hormdee D;Pitiphat W;Boch JA;Izumi Y
无翅蛋白（Wnt）参与胚胎发育、血细胞分化和肿瘤发生。在哺乳动物造血过程中，Wnt 信号传导对于干细胞稳态和淋巴细胞分化至关重要。最近的研究表明，这些分子与心血管疾病、类风湿性关节炎和骨关节炎有关。此外，Wnt5a 信号传导对于人类巨噬细胞的一般炎症反应至关重要。牙周炎是由革兰氏阴性牙周病细菌和由此产生的宿主免疫反应引起的慢性炎症性疾病。牙周炎的特征是牙齿支持结构的丧失和牙槽骨吸收。既往未见牙周炎组织中Wnt5a表达的报道，也仅有少数研究报道LPS刺激的单核细胞中Wnt5a表达的分子机制。使用 RT-PCR，我们证明与健康对照组织相比，慢性牙周炎组织中 Wnt5a mRNA 表达上调。牙龈卟啉单胞菌 LPS 在人单核细胞系 THP-1 中诱导 Wnt5a mRNA，并在刺激后 4 小时达到峰值。牙龈卟啉单胞菌 LPS 诱导 Wnt5a mRNA 的上调程度高于大肠杆菌 LPS。 LPS受体TLR2和TLR4在THP-1细胞表面同等表达。牙龈卟啉单胞菌 LPS 诱导 IκBα 降解，并能够增加 NF-κB 与 DNA 的结合活性。牙龈卟啉单胞菌 LPS 诱导的 Wnt5a 表达被 NF-κB 抑制剂抑制，表明 NF-κB 参与其中。此外，IFN-γ 协同增强牙龈卟啉单胞菌 LPS 诱导的 Wnt5a 产生。药理学研究和siRNA实验表明STAT1对于牙龈卟啉单胞菌LPS诱导的Wnt5a表达很重要。这些结果表明牙龈卟啉单胞菌对Wnt5a表达的调节可能在牙周炎症过程中发挥重要作用，并成为开发新疗法的靶点。
Wingless proteins, termed Wnt, are involved in embryonic development, blood cell differentiation, and tumorigenesis. In mammalian hematopoiesis, Wnt signaling is essential for stem-cell homeostasis and lymphocyte differentiation. Recent studies have suggested that these molecules are associated with cardiovascular diseases, rheumatoid arthritis, and osteoarthritis. Furthermore, Wnt5a signaling is essential for the general inflammatory response of human macrophages. Periodontitis is a chronic inflammatory disease caused by gram-negative periodontopathic bacteria and the resultant host immune response. Periodontitis is characterized by loss of tooth-supporting structures and alveolar bone resorption. There have been no previous reports on Wnt5a expression in periodontitis tissue, and only few study reported the molecular mechanisms of Wnt5a expression in LPS-stimulated monocytic cells. Using RT-PCR, we demonstrated that Wnt5a mRNA expression was up-regulated in chronic periodontitis tissue as compared to healthy control tissue. P. gingivalis LPS induced Wnt5a mRNA in the human monocytic cell line THP-1 with a peak at 4 hrs after stimulation. P. gingivalis LPS induced higher up-regulation of Wnt5a mRNA than E. coli LPS. The LPS receptors TLR2 and TLR4 were equally expressed on the surface of THP-1 cells. P. gingivalis LPS induced IκBα degradation and was able to increase the NF-κB binding activity to DNA. P. gingivalis LPS-induced Wnt5a expression was inhibited by NF-κB inhibitors, suggesting NF-κB involvement. Furthermore, IFN-γ synergistically enhanced the P. gingivalis LPS-induced production of Wnt5a. Pharmacological investigation and siRNA experiments showed that STAT1 was important for P. gingivalis LPS-induced Wnt5a expression. These results suggest that the modulation of Wnt5a expression by P. gingivalis may play an important role in the periodontal inflammatory process and serve a target for the development of new therapies.
登录
查看更多内容
影响因子：
3.5
作者：
JAHNKE, A;JOHNSON, JP
通讯作者：
JOHNSON, JP
影响因子：
3.5
作者：
Fujio, Y;Matsuda, T;Azuma, J
通讯作者：
Azuma, J
影响因子：
6.7
作者：
Bickel, M;Axtelius, B;Attström, R
通讯作者：
Attström, R
DOI：
10.1006/bbrc.2000.3379
发表时间：
2000-09-07
影响因子：
3.1
作者：
Nakashima, T;Kobayashi, Y;Sakai, H
通讯作者：
Sakai, H
DOI：
10.1016/j.bbrc.2007.10.166
发表时间：
2008-01-11
影响因子：
3.1
作者：
Cheng, Ching-wen;Yeh, Ju-ching;Charnock-Jones, D. Stephen
通讯作者：
Charnock-Jones, D. Stephen