The α-tocopherol long-chain metabolite α-13'-COOH affects the inflammatory response of lipopolysaccharide-activated murine RAW264.7 macrophages

Inflammatory response of macrophages is regulated by vitamin E forms. The long-chain metabolite α-13'-carboxychromanol (α-13'-COOH) is formed by hepatic α-tocopherol (α-TOH) catabolism and acts as a regulatory metabolite via pathways that are different from its metabolic precursor METHODS AND RESULTS: : Using semi-synthetically-derived α-13'-COOH we profiled its action on lipopolysaccharide (LPS)-induced expression of pro- and anti-inflammatory genes using RT-qPCR and of key proteins by Western blotting. Effects on inflammatory response were assessed by measuring production of nitric oxide and prostaglandin (PG) E2 , PGD2 and PGF2α . α-13'-COOH inhibits pro-inflammatory pathways in LPS-stimulated RAW264.7 macrophages more efficiently than α-TOH. Profiling inflammation-related genes showed significant blocking of interleukin (Il)1β by the metabolite and its precursor as well, while upregulation of Il6 was not impaired. However, induction of Il10, cyclooxygenase 2 (Cox2) and inducible nitric oxide synthase (iNos) by LPS and consequently the formation of nitric oxide and PG was significantly reduced by α-13'-COOH. Interestingly, α-13'-COOH acted independently from translocation of NFκB subunit p65 CONCLUSION: : Our study sheds new light on the mode of action of α-TOH on the inflammatory response in macrophages, which may be mediated in vivo at least in part by its metabolite α-13'-COOH. Our data show that α-13'-COOH is a potent anti-inflammatory molecule This article is protected by copyright. All rights reserved.