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Grant Abstract

Grant Number: 5R21DE014896-02
PI Name: Kesavalu Lakshmyya
Project Title: n-3 Fatty Acid & Host Responses to Oral Infection

Abstract: 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.

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