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Title: Alpha-Tocopherol alters transcription activities that modulate tumor necrosis factor alpha (TNF-¿)-induced inflammatory response in bovine cells

Author
item Li, Congjun - Cj
item Li, Robert
item Elsasser, Theodore
item Kahl, Stanislaw

Submitted to: Gene Regulation and Systems Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/20/2011
Publication Date: 12/5/2011
Citation: Li, C., Li, R.W., Elsasser, T.H., Kahl, S. 2011. Alpha-Tocopherol alters transcription activities that modulate tumor necrosis factor alpha (TNF-a)-induced inflammatory response in bovine cells. Gene Regulation and Systems Biology. 6:1-14.

Interpretive Summary: We undertook experiment to determining whether vitamin E treatment could modify the inflammatory response. We used microarray technology to profile the gene expression in cells with or without '-tocopherol treatment. We also used bioinformatic analysis to compare the cells response in gene expression. The results showed that vitamin E treatment of cells modulated the cells’ inflammation response. Vitamin E treatment showed a significant opposed effect against inflammatory responses. We concluded vitamin E treatment has a significant biological effect that modulates the cell’s inflammation response by altering the gene expression activities.

Technical Abstract: To further investigate the potential role of '-tocopherol in maintaining immuno-homeostasis in bovine cells (Madin-Darby bovine kidney epithelial cell line), we undertook in vitro experiments using recombinant TNF-a as an immuno-stimulant to simulate inflammation response in cells with and without '-tocopherol pretreatment. Using microarray global profiling and IPA (Ingenuity Pathways Analysis, Ingenuity® Systems, www.ingenuity.com) data analysis on TNF-'-induced gene perturbation in those cells, we focused on determining whether '-tocopherol treatment of normal bovine cells in a standard cell culture condition could modify the immune response of cells induced by a TNF-' challenge. When three datasets were filtered and compared using IPA, there were a total of 1750 genes in all three datasets for comparison: 97 genes were common to all three datasets; 615 genes were common to at least two datasets; there were 261 genes unique in the TNF-' challenge, 399 genes were unique in the '-tocopherol treatment, and 378 genes were unique in the '-tocopherol plus TNF-a treatment. The TNF-' challenge induced significant changes in gene expression. Many of the genes induced by TNF-' are related to the immune and inflammatory responses of cells. The results of the IPA data analysis showed that '-tocopherol pretreatment of cells modulated the cells’ response to the TNF-' challenge. In most of the canonical pathways, '-tocopherol pretreatment showed an antagonistic effect against the TNF-'-induced proinflammatory responses. We concluded that '-tocopherol pretreatment has a significant antagonistic effect that modulates the cell’s response to TNF-' challenges by altering the gene expression activities of some important signaling molecules.