Anti-Inflammatory Effects and Mechanisms of Natural Vitamin E Forms and Their Long-Chain Metabolites

Na young Park, Purdue University

Abstract

Inflammation is the immune response to injury and infection and thus, controlled acute inflammation is a beneficial event required for wound healing, tissue repair, or for defense against invading foreign pathogens. However, prolonged and dysregulated chronic inflammation is mostly harmful and has been linked to many human chronic diseases including cancer. Chronic inflammation involves increased production of proinflammatory mediators, including cytokines, cyclooxygenases (COX-1/COX-2), 5-lipoxygenase (5-LOX), and activation of inflammatory transcription factors such as nuclear factor κB (NF-κB). COX-1/COX-2- and 5-LOX-catalyzed generation of prostaglandins and leukotrienes are key and powerful players for mediating inflammatory response because they stimulate cytokine formation, generate pain and fever, and attract immune cells. In addition, activated NF-κB regulates transcription of over 400 genes associated with inflammation, immunoregulation, and tumor cell proliferation and survival. Therefore, inhibitors that suppress these proinflammatory mediators are believed to be useful for preventing or treating chronic diseases including cancer. Here we show that vitamin E forms and their long-chain metabolites (13’-COOHs) differentially inhibit COX-1/COX-2 and 5-LOX-mediated reactions. Especially, 13’-COOHs have unique anti-inflammatory activities by suppressing both COX-1/COX-2- and 5-LOX-catalyzed proinflammatory pathways. Moreover, we identify a novel anti-NF-κB mechanism by which γ-tocotrienol, a natural form of vitamin E, induces anti-inflammatory A20 by stress adaptive response as a result of modulation of sphingolipids. These specific vitamin E forms and their metabolites might be novel and useful anti-inflammatory agents.

Degree

Ph.D.

Advisors

Jiang, Purdue University.

Subject Area

Nutrition

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