Enhanced expression of vascular endothelial growth factor by periodontal pathogens in gingival fibroblasts
Enhanced expression of vascular endothelial growth factor by periodontal pathogens in gingival fibroblasts
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DOI：
10.1034/j.1600-0765.2003.01646.x
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发表时间：
2003-02-01
影响因子：
3.5
通讯作者：
Izumi, Y
中科院分区：
文献类型：
--
作者：
Suthin, K;Matsushita, K;Izumi, Y
血管内皮生长因子（VEGF）作为一种强有力的血管通透性和血管生成诱导剂，近年来引起了人们的关注。异常血管生成通常与慢性牙周炎的病变形成有关。本研究的目的是探讨VEGF在人牙龈成纤维细胞（HGF）培养中的表达特性。用伴放线放线杆菌和牙龈卟啉单胞菌的脂多糖（LPS）、囊泡（Ve）和外膜蛋白（OMP）刺激HGF。Ve和A. OMP刺激HGF产生VEGF（P < 0.01）。放线菌共生菌和牙龈卟啉单胞菌的浓度为10 μ g/ml或更高。另一方面，VEGF水平不增加LPS刺激。Ve和OMP刺激的HGF中也观察到VEGF mRNA表达。使用豚鼠进行血管通透性增强（VPE）测定以确定来自Ve和OMP刺激的HGF的培养物的上清液是否增强体内血管通透性。Ve和OMP刺激的HGF培养物的上清液强烈诱导VPE。在同时注射抗VEGF多克隆抗体和上清液时，这被显著抑制。刺激物的加热和蛋白酶处理在体外降低Ve和OMP中的VEGF增强水平。这些结果表明，Ve和OMP可能是至关重要的热不稳定性和蛋白酶敏感的牙周病原体，增强VEGF的表达。此外，VEGF可能与牙周炎的病因学在其早期阶段，根据牙周病原体引起肿胀和水肿刺激新生血管。
Vascular endothelial growth factor (VEGF) has recently attracted attention as a potent inducer of vascular permeability and angiogenesis. Aberrant angiogenesis is often associated with lesion formation in chronic periodontitis. The aim of the present study was to investigate the properties of VEGF expression in human gingival fibroblasts (HGF) culture. HGF were stimulated with lipopolysaccharide (LPS), vesicle (Ve) and outer membrane protein (OMP) from Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. HGF constitutively produced VEGF and levels were significantly enhanced (P < 0.01) by stimulation with Ve and OMP from A. actinomycetemcomitans and P. gingivalis at concentrations of 10 mug/ml or higher. On the other hand, VEGF levels were not increased by LPS stimulation. VEGF mRNA expression was also observed in Ve- and OMP-stimulated HGF. A vascular permeability enhancement (VPE) assay was performed using guinea pigs to ascertain whether supernatant from cultures of Ve- and OMP-stimulated HGF enhance vascular permeability in vivo. Supernatant from cultures of Ve- and OMP-stimulated HGF strongly induced VPE. This was markedly suppressed upon simultaneous injection of anti-VEGF polyclonal antibodies with the supernatant. Heating and protease treatment of the stimulants reduced the VEGF enhancing levels in Ve and OMP in vitro. These results suggest that Ve and OMP may be crucial heat-labile and protease-sensitive components of periodontal pathogens that enhance VEGF expression. In addition, VEGF might be associated with the etiology of periodontitis in its early stages according to neovascularization stimulated by periodontal pathogens causing swelling and edema.