Nutrition

Biography

Biography: Joan Cook-Mills

Abstract

Asthma is a heterogeneous disease resulting from complex interactions of environmental and genetic factors. The World Health Organization reported that the prevalence of asthma has increased over only a few decades suggesting an important role of the local environment. One environmental change over the past 40 years has been an increase in the d-γ-tocopherol isoform of vitamin E in the diet and in infant formulas. Our studies focus on regulation of allergic inflammation by the two most abundant forms of vitamin E (d-α-tocopherol and d-γ-tocopherol) in the diet and tissues. We demonstrated that α-tocopherol inhibits and γ-tocopherol elevates leukocyte recruitment across endothelium in vitro and endothelial cell protein kinase Cα activation for eosinophil and dendritic cell recruitment during allergic inflammation. Specifically, γ-tocopherol is an agonist and α-tocopherol is an antagonist of PKC . In vivo, α-tocopherol supplementation blocks eosinophilic allergic lung responses in adult mice and that α-tocopherol associates with better lung spirometry in adult humans. Notably, γ-tocopherol has the opposite function. In humans, a 5-fold higher plasma γ-tocopherol level associates with lower lung spirometry in adults by age 21, suggesting tocopherol isoforms have a regulatory role early in life. In clinical studies and animal models, offspring of allergic mothers have increased responsiveness to allergen challenge. We demonstrated that development of allergic responses in offspring is inhibited or elevated by maternal supplementation with α-tocopherol or γ- tocopherol, respectively. These results have implications for supplementation of allergic mothers with tocopherol isoforms and for development of allergies in future generations. Grant Support: NIH R01HL111624.