CXCL12 and CXCR4 expression by human gingival fibroblasts in periodontal disease
CXCL12 and CXCR4 expression by human gingival fibroblasts in periodontal disease
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DOI：
10.1111/j.1365-2249.2005.02852.x
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发表时间：
2005-09-01
影响因子：
4.6
通讯作者：
Matsuo, T
中科院分区：
文献类型：
--
作者：
Hosokawa, Y;Hosokawa, I;Matsuo, T
CXCL12是一种CXC趋化因子，与关节炎等炎症部位的淋巴细胞浸润和血管生成有关。然而，CXCL12在牙周疾病中的表达和作用尚不确定。本研究的目的是评估牙周组织中CXCL12及其受体CXCR4的表达，并研究人牙龈成纤维细胞（HGF）表达CXCL12和CXCR4的特性。 RT-PCR分析显示CXCL12和CXCR4 mRNA在正常牙龈组织和牙周病变组织中均有表达。免疫组织化学显示，正常牙龈组织和牙周病牙龈组织中均表达CXCL12，并发现CXCR4阳性细胞。我们的体外实验阐明，HGF 持续产生 CXCL12，并且通过肿瘤坏死因子-α (TNF-α)、干扰素-γ (IFN-γ)、转化生长因子-β (TGF-β)、正常 T 细胞表达和分泌的激活调节 (RANTES) 和巨噬细胞炎症蛋白 3 刺激，其水平得到增强。 α（MIP-3 α）。另一方面，热灭活的牙龈卟啉单胞菌（P. gingivalis）和牙龈卟啉单胞菌LPS减少了HGF产生的CXCL12。流式细胞术分析表明CXCR4在HGF上高表达，并且CXCR4表达被TNF-α、IFN-γ和牙龈卟啉单胞菌LPS消除。此外，CXCL12 诱导 HGF 产生血管内皮生长因子 (VEGF)。我们的结果表明，CXCL12可能与正常牙周组织和牙周病变组织中CXCR4(+)细胞的浸润和血管生成有关。牙龈卟啉单胞菌是一种已知的牙周病原体，可通过 HGF 抑制 CXCL12 的产生和 CXCR4 的表达。这一事实意味着牙龈卟啉单胞菌可能抑制牙周组织中CXCR4(+)细胞的浸润和新生血管形成并逃避免疫反应。
CXCL12 is a CXC chemokine that is related to lymphocyte infiltration and angiogenesis in inflammatory sites such as arthritis. However, the expression and roles of CXCL12 in periodontal disease are uncertain. The aim of this study was to assess the expression of CXCL12 and its receptor, CXCR4, in periodontal tissue and to investigate the properties of CXCL12 and CXCR4 expression by human gingival fibroblasts (HGF). RT-PCR analysis revealed that CXCL12 and CXCR4 mRNA were expressed in both normal gingival tissues and periodontal diseased tissues. Immunohistochemistry disclosed that CXCL12 was expressed and CXCR4 positive cells were found in both normal and periodontal diseased gingival tissues. Our in vitro experiments elucidated that HGF constitutively produced CXCL12, and the levels were enhanced by stimulation with tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), regulated upon activation normal T cell expressed and secreted (RANTES) and macrophage inflammatory protein 3 alpha (MIP-3 alpha). On the other hand, heat killed Porphyromonas gingivalis (P. gingivalis) and P. gingivalis LPS reduced the CXCL12 production by HGF. Flow cytometry analysis clarified that CXCR4 was highly expressed on HGF, and CXCR4 expression was abrogated by TNF-alpha, IFN-gamma and P. gingivalis LPS. Moreover, CXCL12 induced vascular endothelial growth factor (VEGF) production by HGF. Our results demonstrated that CXCL12 might be related to CXCR4(+) cells infiltration and angiogenesis both in normal periodontal tissues and periodontal diseased tissue. P. gingivalis, a known periodontal pathogen, inhibits the production of CXCL12 and the expression of CXCR4 by HGF. This fact means that P. gingivalis may inhibit CXCR4(+) cells infiltration and neovascularization in periodontal tissue and escape from the immune response.