Isoforms of vitamin E differentially regulate inflammation and lung function (P5136)

Abstract

Abstract Vitamin E regulation of disease has been extensively studied but most studies focus on the α-tocopherol isoform of vitamin E. These reports indicate contradictory outcomes for anti-inflammatory functions of the α-tocopherol isoform of vitamin E with regards to animal and clinical studies. The seemingly disparate results are consistent with our studies demonstrating that purified natural forms of vitamin E have opposing regulatory functions during inflammation. We have determined that α-tocopherol inhibits whereas γ-tocopherol elevates allergic inflammation, airway hyperresponsiveness, leukocyte transendothelial migration, and endothelial cell adhesion molecule signaling through protein kinase Cα. Moreover, we determined that α-tocopherol is an antagonist and γ-tocopherol is an agonist of PKCα through direct binding to a regulatory domain of PKCα. Furthermore, in a recent clinical study, we determined that increasing serum concentrations of γ-tocopherol associated with worse lung function, while increasing serum concentrations of α-tocopherol associated with better lung function. In summary, we have determined mechanisms for opposing regulatory functions of α-tocopherol and γ-tocopherol on inflammation. Information from our studies will have significant impact on the design of clinical studies on inflammation and on vitamin E consumption.