Angiopoietin-like protein 2 regulates Porphyromonas gingivalis lipopolysaccharide-induced inflammatory response in human gingival epithelial cells.
Angiopoietin-like protein 2 regulates Porphyromonas gingivalis lipopolysaccharide-induced inflammatory response in human gingival epithelial cells.
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DOI：
10.1371/journal.pone.0184825
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Mitani A
中科院分区：
文献类型：
--
作者：
Ohno T;Yamamoto G;Hayashi JI;Nishida E;Goto H;Sasaki Y;Kikuchi T;Fukuda M;Hasegawa Y;Mogi M;Mitani A
血管生成素样蛋白2（ANGPTL 2）通过诱导炎症和血管生成来维持组织稳态。它产生于浸润性免疫细胞或驻留细胞，如脂肪细胞、血管内皮细胞和肿瘤细胞。我们假设ANGPTL 2可能作为系统性疾病和牙周疾病的独特介质发挥重要作用。我们证明了慢性牙周炎患者龈沟液中ANGPTL 2浓度增加。牙龈卟啉单胞菌脂多糖（LPS）处理强烈诱导Ca 9 -22人牙龈上皮细胞中ANGPTL 2 mRNA和蛋白水平。重组人ANGPTL 2增加Ca 9 -22细胞中白细胞介素1β（IL-1β）、IL-8和肿瘤坏死因子-α（TNF-α）的mRNA和蛋白水平。在牙龈卟啉单胞菌LPS刺激的Ca 9 - 22细胞中，与对照siRNA相比，Ca 9 -22细胞中小干扰（si）RNA介导的ANGPTL 2敲低降低了IL-1β、IL-8和TNF-α mRNA和蛋白水平（p<0.01）。针对整联蛋白α5β1（一种ANGPTL受体）的抗体阻断牙龈卟啉单胞菌LPS处理的Ca 9 -22细胞中这些炎性细胞因子的诱导，表明分泌的ANGPTL通过自分泌环诱导牙龈上皮细胞中的炎性细胞因子。牙龈卟啉单胞菌LPS →炎性细胞因子诱导的经典顺序级联反应已得到充分确立。然而，在目前的研究中，我们揭示了一种新的级联反应，包括牙龈卟啉单胞菌LPS → ANGPTL 2 →整合素α5β1 →炎性细胞因子诱导，这可能是导致牙龈上皮细胞中有效的牙周组织解体活性的原因。通过这一途径，ANGPTL 2在牙周炎的发病机制中发挥作用，并有助于延长全身性疾病患者的慢性炎症。
Angiopoietin-like protein 2 (ANGPTL2) maintains tissue homeostasis by inducing inflammation and angiogenesis. It is produced in infiltrating immune cells or resident cells, such as adipocytes, vascular endothelial cells, and tumor cells. We hypothesized that ANGPTL2 might play an important role as a unique mediator in both systemic and periodontal disease. We demonstrated an increased ANGPTL2 concentration in gingival crevicular fluid from chronic periodontitis patients. Porphyromonas gingivalis lipopolysaccharide (LPS) treatment strongly induced ANGPTL2 mRNA and protein levels in Ca9-22 human gingival epithelial cells. Recombinant human ANGPTL2 increased interleukin 1β (IL-1β), IL-8, and tumor necrosis factor-α (TNF-α) mRNA and protein levels in Ca9-22 cells. Small-interfering (si)RNA-mediated ANGPTL2 knockdown in Ca9-22 cells reduced IL-1β, IL-8 and TNF-α mRNA and protein levels compared with control siRNA (p<0.01) in P. gingivalis LPS-stimulated Ca9-22 cells. Antibodies against integrin α5β1, an ANGPTL receptor, blocked induction of these inflammatory cytokines in P. gingivalis LPS-treated Ca9-22 cells, suggesting that secreted ANGPTL induces inflammatory cytokines in gingival epithelial cells via an autocrine loop. The classic sequential cascade of P. gingivalis LPS → inflammatory cytokine induction is well established. However, in the current study, we reveal a novel cascade comprising sequential P. gingivalis LPS → ANGPTL2 → integrin α5β1 → inflammatory cytokine induction, which might be responsible for inducing potent periodontal disorganization activity in gingival epithelial cells. Via this pathway, ANGPTL2 functions in the pathogenesis of periodontitis and contributes to prolonging chronic inflammation in patients with systemic disease.
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影响因子：
3.7
作者：
Goto H;Ishihara Y;Kikuchi T;Izawa A;Ozeki N;Okabe E;Kamiya Y;Ozawa Y;Mizutani H;Yamamoto G;Mogi M;Nakata K;Maeda H;Noguchi T;Mitani A
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