|Zingg, Jean-Marc -|
|Han, Sung Nim -|
|Pang, Eunice -|
|Meydani, Mohsen -|
|Meydani, Simin -|
|Azzi, Angelo -|
Submitted to: Archives Of Biochemistry and Biophysics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 19, 2013
Publication Date: October 15, 2013
Citation: Zingg, J., Han, S., Pang, E., Meydani, M., Meydani, S.N., Azzi, A. 2013. In vivo regulation of gene transcription by alpha- and gamma-Tocopherol in murine T lymphocytes. Archives Of Biochemistry and Biophysics. 538(2):111-119. Interpretive Summary: There are actually eight known molecules designated as vitamin E. One known as alpha-T (tocopherol), is abundant in the European diet, and has been studied the most. Another one called gamma-T (tocopherol) is abundant in the American diet. We compared the effects both of these forms of vitamin E on immune response by supplementing mouse chow with low and high doses of each of the isomers. We specifically studied the impact on T lymphocytes, which protect against infection and tumors. The results indicated that there was a significant difference between the effect of alpha-T and gamma-T on T cell gene expression and function. This showed that the American and European diet may protect against infections in different ways.
Technical Abstract: Of the 8 different analogues (alpha-, beta-, gamma-, delta-tocopherols and tocotrienols) designated as vitamin E, alpha-tocopherol (a-T) has been mostly studied, together with gamma-tocopherol (g-T) which is abundant in the US diet. We compared the effect of dietary supplementation with adequate or high doses of alpha-T or g-T on the number and type of genes expressed following T cell activation. C57BL/6 mice were fed diets containing adequate (30 PPM) or high (500 PPM) amounts of a-T or g-T for 4 weeks. Spleen T cells were stimulated ex vivo with plate-bound anti-CD3 and soluble anti-CD28, and gene expression changes were assessed by gene array analysis. The data obtained indicated significant qualitative and quantitative differences between the two analogs in regulating gene expression induced by T cell stimulation. Genes were found uniquely responding to either high a-T (e.g. induced: CD40 ligand, lymphotoxin A) or g-T (e.g. repressed: poliovirus receptor-related-2). Interestingly, in stimulated T-cells from mice supplemented with high amounts of a-T a bigger number of genes were activated than in mice supplemented with the same amounts of g-T; under the same conditions g-T repressed the expression of a number of genes larger than a-T. It is possible that the observed diminution in gene expression in T cells after high g-T in vivo supplementation modulates inflammation or other T cell mediated functions.