Proinflammatory effects of tumour necrosis factor-like weak inducer of apoptosis (TWEAK) on human gingival fibroblasts
Proinflammatory effects of tumour necrosis factor-like weak inducer of apoptosis (TWEAK) on human gingival fibroblasts
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DOI：
10.1111/j.1365-2249.2006.03233.x
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发表时间：
2006-12-01
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.
肿瘤坏死因子样弱诱导因子是肿瘤坏死因子家族的一员，是一种调节细胞增殖、血管生成、炎症和细胞凋亡的多功能细胞因子。在这项研究中，我们研究了TWEW在牙周病组织中的表达以及TWEW对人牙龈成纤维细胞(HGF)的影响。逆转录-聚合酶链式反应(RT-PCR)和免疫组织化学分析表明，TWEEP及其受体、成纤维细胞生长因子诱导因子14(Fn14)的mRNA和蛋白在牙周病组织中均有表达。HGF表达Fn14，产生IL-8和血管内皮生长因子(VEGF)，并呈剂量依赖关系。转化生长因子(TGF)-β1或IL-1β同时刺激可协同增强TWEAM诱导的IL-8和VEGF的产生。IL-1β和转化生长因子-β1以剂量依赖的方式促进Fn14的表达。此外，TWeak还以剂量依赖的方式诱导HGF表达细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)。TWEK诱导的ICAM-1表达可被转化生长因子-β1增强，而TWEW诱导的VCAM-1表达则被抑制。磷脂酰肌醇3-激酶(PI3K)和核因子-kappaB(NF-kappaB)抑制剂可抑制TWEW诱导的ICAM-1和VCAM-1的表达。然而，丝裂原活化蛋白激酶(MEK)和c-jun氨基末端激酶(JNK)抑制剂仅增强HGF上VCAM-1的表达。这些结果提示，TWEEP可能参与了牙周病的病理生理过程。此外，TWEK与IL-1β或转化生长因子-β1结合，可能与HGF诱导的促炎细胞因子和黏附分子在牙周病的加重有关。
Tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), a member of the TNF family, is a multi-functional cytokine that regulates cellular proliferation, angiogenesis, inflammation and apoptosis. In this study, we investigated TWEAK expression in periodontally diseased tissues and the effect of TWEAK on human gingival fibroblasts (HGF). Reverse transcription-polymerase chain reaction (RT-PCR) analysis and immunohistochemistry revealed that TWEAK and the TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14), mRNA and protein were expressed in periodontally diseased tissues. HGF expressed Fn14 and produced interleukin (IL)-8 and vascular endothelial growth factor (VEGF) production upon TWEAK stimulation in a dose-dependent manner. The IL-8 and VEGF production induced by TWEAK was augmented synergistically by simultaneous stimulation with transforming growth factor (TGF)-beta 1 or IL-1 beta. IL-1 beta and TGF-beta 1 enhanced Fn14 expression in a dose-dependent manner. Moreover, TWEAK induced intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression on HGF in a dose-dependent manner. The ICAM-1 expression induced by TWEAK was augmented by TGF-beta 1. On the other hand, the TWEAK-induced VCAM-1 expression was inhibited by TGF-beta 1. Phosphatidylinositol 3-kinase (PI3K) and nuclear factor-kappaB (NF-kappa B) inhibitor inhibit both ICAM-1 and VCAM-1 expression induced by TWEAK. However, mitogen-activated protein kinase (MEK) and c-Jun NH2-terminal kinase (JNK) inhibitor enhanced only VCAM-1 expression on HGF. These results suggest that TWEAK may be involved in the pathophysiology of periodontal disease. Moreover, in combination with IL-1 beta or TGF-beta 1, TWEAK may be related to the exacerbation of periodontal disease to induce proinflammatory cytokines and adherent molecules by HGF.