1a. Objectives (from AD-416)
LAB: NUTRITIONAL IMMUNOLOGY 1. Investigate the molecular and cellular basis of age-related decline in T cell function and its reversal by vitamin E. a) Determine the mechanisms of Vitamin E-induced enhancement of T cell function in the aged with focus on early activation signaling and membrane related events. b) Determine the contribution of polymorphisms at cytokine genes to heterogeneity of vitamin E-induced effects on cytokine production and resistance to respiratory infections. 2. Determine the effect of reducing caloric intake on the immune response of humans. LAB: VASCULAR BIOLOGY 1. Identify bioactive food components and food patterns that inhibit atherosclerosis and angiogenesis using cell culture and animal models under the following sub-objectives: a) Determine bioavailability of avenanthramides from oats and characterize their potency and molecular mechanism of inhibition of vascular smooth muscle cell proliferation using cell culture systems and the femoral artery injury mouse model. b) Elucidate the molecular mechanism of catechins and curcumin and other dietary bioactive compounds on the inhibition of angiogenesis associated with adipose tissue growth and obesity. c) Determine the comparative bioavailability and biopotency of tocopherols versus tocopheryl phosphate on the inhibition of femoral artery injury model of vascular atherosclerosis and restenosis. 2. Determine the anti-inflammatory and anti-proliferative effects of avenanthramides of oats and derivatives on several colonic cancer cells lines and mouse models of inflammatory bowel disease and colon cancer.
1b. Approach (from AD-416)
LAB: NUTRITIONAL IMMUNOLOGY T cell function declines with age resulting in higher incidence of infections in the elderly. We showed that vitamin E (E) supplementation enhances T cell function in the aged. In Objective 1-A, we will test the hypothesis that T cell receptor (TCR)-induced signalosomes (combination of protein and lipids that are formed at the site of T cell and antigen presenting cells) exhibit age- and vitamin E (E)-related differences in their patterns of protein and lipid recruitment. We will identify qualitative and quantitative age- and E-related differences in the protein and lipid composition of signalosomes using an enhanced magnetic immunoisolation procedure and highly sensitive and quantitative proteomics and lipidomics methods. In objective 1-B, we will test the hypothesis that higher frequencies of specific cytokine polymorphisms contribute to incidence and severity of respiratory infection (RI) in the aged and that the effect of E on RI is dependent on cytokine genotype. This will be tested using data and DNA samples collected from a 1-year randomized, double-blind, controlled (RTC) study of E supplementation in elderly. In Objective 2 we will test the hypothesis that a long- term calorie restriction (CR) intervention in humans will enhance T cell-mediated function and that the CR- mediated effect is due to intrinsic changes in T cells and/or a reduction in prostaglandin PGE2 production. This hypothesis will be tested utilizing subjects enrolled in the NIA- supported multi-center RTC, CALERIE Phase 2 and determining the effect of CR on T cell subsets proliferation, and intra- and extra-cellular cytokine, and PGE2 levels before, and following 1 and 2 years of 25% CR. These studies will help develop effective strategies to improve the immune response in the elderly. LAB: VASCULAR BIOLOGY The main objective of this project plan is to determine bioavailability, potency and mechanism of action of several bioactive food components, including avenanthramides (Avns) of oats, curcumin of turmeric, catechins of green tea and isomers of tocopherol in the prevention of atherosclerosis and angiogenesis as they relate to CVD, obesity and cancer. Specifically, we will determine bioavailability of Avns from oats and characterize their potency and mechanism of inhibition of vascular smooth muscle cell proliferation using cell culture and the femoral artery injury mouse model. Further, we will investigate the anti-inflammatory and anti-proliferative effects of Avns of oats and derivatives on several cancer cells lines and mouse models of inflammatory bowel disease and colon cancer. We will also elucidate the molecular mechanism of catechins and curcumin and other dietary bioactive compounds on the inhibition of angiogenesis associated with adiposity and obesity. We also plan to investigate the comparative biopotency of' alpha-tocopherol (alpha-T) versus alpha-tocopheryl phosphate (alpha-TP) on the inhibition inflammatory cytokines and monocyte adhesion in cell culture systems and on comparative bioavailability and efficacy of alpha-T vs. alpha-TP on femoral artery injury model of atherosclerosis.
3. Progress Report
This new Project Plan was recently certified through ARS Office of Scientific Quality Review (OSQR) and will report progress in 2010-2014. For further details on current work see the 2009 report for project 1950-51000-058-00D.
1. This new Project Plan was recently certified through ARS Office of Scientific Quality Review (OSQR) and will report accomplishments in 2010-2014. For further details on current accomplishments see the 2009 report for project 1950-51000-058-00D.