Luteolin inhibits lipopolysaccharide actions on human gingival fibroblasts
Luteolin inhibits lipopolysaccharide actions on human gingival fibroblasts
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DOI：
10.1016/j.ejphar.2006.03.069
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发表时间：
2006-07-10
影响因子：
5
通讯作者：
Maldonado-Frias, Silvia
中科院分区：
文献类型：
--
作者：
Gutierrez-Venegas, Gloria;Kawasaki-Cardenas, Perla;Maldonado-Frias, Silvia
牙周病包括一组感染，导致牙龈炎症，牙周组织破坏，在严重的情况下，伴有牙槽骨丢失和牙齿脱落。伴放线放线杆菌（Actinobacillusactinomycetemcomitans）是一种革兰氏阴性微生物，其具有并产生在疾病发展中起关键作用的脂多糖（lipopolysaccharide，LPS）分子。人牙龈成纤维细胞是牙龈结缔组织的主要成分，并可与细菌和细菌产物（包括LPS）直接相互作用。黄酮类化合物具有抗氧化和抗炎特性，可减少巨噬细胞和单核细胞中的炎症分子表达。本研究评价了不同黄酮类化合物对LPS刺激的人牙龈成纤维细胞产生一氧化氮的调节作用，并研究了木犀草素对丝裂原活化蛋白激酶（MAPK）家族成员磷酸化的抑制作用以及对蛋白激酶B（Akt）、核因子κ B（NF-kappa B）活化、诱导型一氧化氮合酶（NOS）表达和一氧化氮（NO）合成的影响。我们还发现，预处理与三种黄酮类化合物，包括槲皮素，染料木素，和毛地黄黄酮，阻断一氧化氮的合成，在剂量依赖性的方式。木犀草素对这种炎症介质的表达具有最强的阻断作用。木犀草素预处理减弱LPS诱导的细胞外信号调节激酶p38和Akt磷酸化。LPS处理人牙龈成纤维细胞导致NF-κ B易位。用木犀草素预处理细胞可消除LPS对NF-κ B易位的影响。此外，毛地黄黄酮治疗阻断LPS诱导的细胞增殖抑制，而不影响遗传物质的完整性。我们的结论是，毛地黄黄酮干扰LPS信号通路，减少几个丝裂原活化蛋白激酶家族成员的激活，并抑制炎症介质的表达。(c)2006 Elsevier B. V.保留所有权利。
Periodontal disease comprises a group of infections that lead to inflammation of the gingiva, periodontal tissue destruction, and in severe cases is accompanied by alveolar bone loss with tooth exfoliation. Actinobacillus actinomycetemcomitans is a Gram-negative microorganism, which possesses and produces lipopolysaccharide (LPS) molecules that play a key role in disease development. Human gingival fibroblasts are the major constituents of gingival connective tissue and may interact directly with bacteria and bacterial products including LPS. Flavonoids possess antioxidant and anti-inflammatory properties that reduce inflammatory molecule expression in macrophages and monocytes. In this study, we evaluated the ability of diverse flavonoids to regulate nitric oxide production of LPS-stimulated human gingival fibroblasts, and studied the effect of luteolin on diminish phosphorylation in mitogen-activated protein kinase (MAPK) family members as well as in protein kinase B (Akt), nuclear factor kappa B (NF-kappa B) activation, inducible nitric oxide synthase (NOS) expression, and nitric oxide (NO) synthesis. We also found that pretreatment with three flavonoids, including quercetin, genistein, and luteolin, blocked nitric oxide synthesis in a dose-dependent fashion. Luteolin exerted the strongest blocking action on expression of this inflammatory mediator. Luteolin pretreatment attenuated LPS-induced extracellular signal-regulated kinase, p38, and Akt phosphorylation. LPS treatment of human gingival fibroblasts resulted in NF-kappa B translocation. Cell pretreatment with luteolin abolished LPS effects on NF-kappa B translocation. In addition, luteolin treatment blocked LPS-induced cellular proliferation inhibition without affecting genetic material integrity. We concluded that luteolin interferes with LPS signaling pathways, reducing activation of several mitogen-activated protein kinase family members, and inhibits inflammatory mediator expression. (c) 2006 Elsevier B.V. All rights reserved.