Proinflammatory effects of muramyldipeptide on human gingival fibroblasts
Proinflammatory effects of muramyldipeptide on human gingival fibroblasts
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DOI：
10.1111/j.1600-0765.2009.01217.x
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发表时间：
2010-04-01
影响因子：
3.5
通讯作者：
Matsuo, T.
中科院分区：
文献类型：
--
作者：
Hosokawa, I.;Hosokawa, Y.;Matsuo, T.
背景和目的：由于人牙龈成纤维细胞（HGF）是牙周组织中的主要细胞，我们假设 HGF 与细菌成分的受体有关。在本研究中，我们重点关注HGF中核苷酸结合寡聚结构域2（NOD2）的表达和功能，HGF是一种哺乳动物细胞质病原体识别分子。材料和方法：通过逆转录酶聚合酶链反应（RT-PCR）和流式细胞术检测HGF中NOD2的表达。通过酶联免疫吸附测定 (ELISA) 检查 HGF 中白细胞介素 (IL)-6、IL-8、cc 趋化因子配体 2、cxc 趋化因子配体 10 (CXCL10) 和 CXCL11 的产生。我们采用RT-PCR和免疫组化方法检测人牙龈组织中NOD2的表达。结果：我们发现HGFs中有明确的NOD2表达。在用 NOD2 激动剂胞壁酰二肽 (MDP) 刺激后，促炎细胞因子的产生增强。此外，丝裂原激活蛋白激酶抑制剂和磷脂酰肌醇3激酶抑制剂以不同的方式抑制MDP诱导的促炎细胞因子的产生。此外，MDP 通过肿瘤坏死因子-α (TNF-α) 或干扰素-γ (IFN-γ) 刺激的 HGF 增强了 CXCL10 和 CXCL11 的产生，尽管单独使用 MDP 并不能诱导这些趋化因子。 TNF-α 和 IFN-γ 增加 HGF 中 NOD2 的表达。此外，我们还检测了牙周病组织中单核细胞和HGFs中NOD2的表达。结论：这些结果表明，MDP诱导HGFs产生细胞因子和趋化因子，与牙周病的发病机制有关。
Background and Objective:Because human gingival fibroblasts (HGFs) are the predominant cells in periodontal tissues, we hypothesized that HGFs are contributed to receptors for components of bacteria. In this study, we focused on expression and function of nucleotide binding oligomerization domain 2 (NOD2) in HGFs, which is a mammalian cytosolic pathogen recognition molecule.Material and Methods:Expression of NOD2 in HGFs was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry. Production of interleukin (IL)-6, IL-8, cc chemokine ligand2, cxc chemokine ligand10 (CXCL10) and CXCL11 from HGFs was examined by enzyme-linked immunosorbent assay (ELISA). We used RT-PCR and immunohistochemistry to detect the NOD2 expression in human gingival tissues.Results:We found clear NOD2 expression in HGFs. Upon stimulation with NOD2 agonist, muramyldipeptide (MDP), production of proinflammatory cytokines was enhanced. Moreover, MDP-induced production of proinflammatory cytokines was inhibited in a different manner by mitogen-activated protein kinase inhibitors and phosphatidylinositol 3-kinase inhibitor. Furthermore, MDP enhanced CXCL10 and CXCL11 productions by tumor necrosis factor-alpha (TNF-alpha)- or interferon-gamma (IFN-gamma)-stimulated HGFs, although MDP alone did not induce these chemokines. TNF-alpha and IFN-gamma increased NOD2 expression in HGFs. In addition, we detected NOD2 expression in mononuclear cells and HGFs in periodontally diseased tissues.Conclusion:These findings indicate that MDP which induces production of cytokines and chemokines from HGFs is related to the pathogenesis of periodontal disease.