n-3 Fatty Acid & Host Responses to Oral Infection

描述（由申请人提供）：本R21申请的主要目的是在动物模型中探索饮食n-3多不饱和脂肪酸（PUFA）调节对体内Pg口腔感染的分子宿主反应的潜在作用。很明显，宿主促炎介质对慢性炎症中的组织破坏有显著贡献。膳食n-3脂肪酸已被证明通过调节人类和啮齿动物中的淋巴细胞增殖、细胞因子产生、信号转导和基因表达来调节炎症反应;通过减少炎症性疾病、心血管疾病、增加对乳腺癌、结肠癌、胰腺肿瘤的抗肿瘤作用以及改善细菌和自身免疫反应来提供益处。因此，我们将首先关注n-3 PUFA，这是“鱼油”中的主要膳食脂质。“我们将确定其作为牙周病原体原型改变宿主反应，影响Pg发病机制的能力。实验将利用感染和牙槽骨吸收的体内啮齿动物模型。 大量的证据已经确定了宿主来源的炎性细胞因子在牙周炎症和疾病中的作用，牙周炎症和疾病可以导致牙槽骨损失和随后的牙齿损失，这是牙周炎的特征。据了解，目前还没有体内研究评价n-3多不饱和脂肪酸如何调节牙周病牙龈组织和牙槽骨吸收中特定宿主细菌的相互作用。为检验这一假设而设计的两个具体目标：1）检查饮食n-3 PUFA对牙龈组织中促炎性细胞因子表达的影响，（TNF α、IL-1b、IL-6、脂质过氧化物、TBARS），抗炎（IL-10、TGF-β 1、抗氧化剂）生物分子和T细胞表型（2）研究n-3脂肪酸对Pg定植和牙槽骨吸收的影响。这个营养和口腔感染项目的长期目标是帮助理解使膳食n-3脂肪酸能够改善牙周病发病机制的组织破坏方面的细胞和分子机制。积极的研究结果可以使改善饮食策略作为预防牙周病的有效手段。

DESCRIPTION (provided by applicant): The major objectives of this R21 application are to explore the potential role of dietary n-3 polyunsaturated fatty acid (PUFA) regulation on molecular host responses to oral infection with Pg in vivo in an animal model. It is clear that host pro-inflammatory mediators provide a significant contribution to tissue destruction in chronic inflammation. Dietary n-3 fatty acid has been shown to modulate inflammatory responses via regulating lymphocyte proliferation, cytokine production, signal transduction, and gene expression in humans and rodents; providing a benefit by reducing inflammatory disorders, cardiovascular diseases, increasing anti tumorigenic effects on breast cancer, colon cancer, pancreatic neoplasms, and improving bacterial and autoimmune responses. Thus, we will initially focus on n-3 PUFA, which is the primary dietary lipid in "fish oil." We will determine its capability to modify host responses, affecting Pg pathogenesis, as a prototype periodontal pathogen. The experiments will utilize an in vivo rodent model of infection and alveolar bone resorption. Substantial evidence has established the contribution of host derived inflammatory cytokines in periodontal inflammation and disease that can lead to the alveolar bone loss and subsequent tooth loss, characteristic of periodontitis. To5knowledge, there are no in vivo investigations evaluating how n-3 PUFA regulates specific host-bacterial interactions in gingival tissues and alveolar bone resorption in periodontal disease. Two Specific Aims designed to test this hypothesis: 1) To examine the effect of dietary n-3 PUFA on gingival tissue expression of proinflammatory (TNFa, IL-1b,IL-6, lipid per oxidation, TBARS), anti-inflammatory (IL-10, TGF-b1, antioxidants) biomolecules, and T cell phenotypes (Th1, Th2) induced by Pg infection, and 2) To determine the effects of dietary n-3 fatty acid on Pg colonization and alveolar bone resorption. The long-range goal of this nutrition and oral infection project is to contribute to understanding the cellular and molecular mechanisms that enable dietary n-3 fatty acid to ameliorate tissue destructive aspects of periodontal pathogenesis. Positive findings could enable improved dietary strategies as adjuncts in the prevention of periodontal disease.