Bodet C, La V D, Epifano F, Grenier D
Groupe de Recherche en Ecologie Buccale, Faculté de Médecine Dentaire, Université Laval, Quebec City, Quebec G1K 7P4, Canada.
J Periodontal Res. 2008 Aug;43(4):400-7. doi: 10.1111/j.1600-0765.2007.01055.x.
Periodontitis is a chronic inflammatory disease of bacterial etiology, affecting tooth-supporting tissues. The host inflammatory response to periodontopathogens, notably the high and continuous production of cytokines, is considered a major factor causing the local tissue destruction observed in periodontitis. The aim of the present study was to investigate the effect of naringenin, a major flavanone in grapefruits and tomatoes, on the lipopolysaccharide-induced pro-inflammatory cytokine production by host cells, using two different models.
The effect of naringenin was characterized using macrophages stimulated with the lipopolysaccharide of either Aggregatibacter actinomycetemcomitans or Escherichia coli and using whole blood stimulated with A. actinomycetemcomitans lipopolysaccharide, in the presence or absence of naringenin. Lipopolysaccharide-induced interleukin-1 beta, interleukin-6, interleukin-8 and tumor necrosis factor-alpha production by macrophages and whole-blood samples treated with naringenin were evaluated using an enzyme-linked immunosorbent assay. Changes in the phosphorylation states of macrophage kinases induced by A. actinomycetemcomitans lipopolysaccharide and naringenin were characterized by immunoblot screening.
Our results clearly indicated that naringenin is a potent inhibitor of the pro-inflammatory cytokine response induced by lipopolysaccharide in both macrophages and in whole blood. Naringenin markedly inhibited the phosphorylation on serines 63 and 73 of Jun proto-oncogene-encoded AP-1 transcription factor in lipopolysaccharide-stimulated macrophages.
The results from the present study suggest that naringenin holds promise as a therapeutic agent for treating inflammatory diseases such as periodontitis.
牙周炎是一种由细菌引起的慢性炎症性疾病，会影响牙齿支持组织。宿主对牙周病原体的炎症反应，尤其是细胞因子的持续大量产生，被认为是导致牙周炎中局部组织破坏的主要因素。本研究的目的是使用两种不同模型，研究柚皮素（葡萄柚和番茄中的一种主要黄烷酮）对脂多糖诱导的宿主细胞促炎细胞因子产生的影响。
在有或没有柚皮素的情况下，使用牙龈卟啉单胞菌或大肠杆菌的脂多糖刺激的巨噬细胞以及用牙龈卟啉单胞菌脂多糖刺激的全血来表征柚皮素的作用。使用酶联免疫吸附测定法评估用柚皮素处理的巨噬细胞和全血样本中脂多糖诱导的白细胞介素-1β、白细胞介素-6、白细胞介素-8和肿瘤坏死因子-α的产生。通过免疫印迹筛选来表征牙龈卟啉单胞菌脂多糖和柚皮素诱导的巨噬细胞激酶磷酸化状态的变化。
我们的结果清楚地表明，柚皮素是脂多糖在巨噬细胞和全血中诱导的促炎细胞因子反应的有效抑制剂。柚皮素显著抑制脂多糖刺激的巨噬细胞中原癌基因编码的AP-1转录因子Jun丝氨酸63和73位的磷酸化。
本研究结果表明，柚皮素有望作为治疗牙周炎等炎症性疾病的治疗剂。
