alpha -Tocopherol long-chain metabolite-13'-COOH affects the inflammatory response of lipopolysaccharide-activated murine RAW264.7 macrophages

ScopeInflammatory response of macrophages is regulated by vitamin E forms. The long-chain metabolite -13-carboxychromanol (-13-COOH) is formed by hepatic -tocopherol (-TOH) catabolism and acts as a regulatory metabolite via pathways that are different from its metabolic precursor. Methods and resultsUsing semisynthetically-derived -13-COOH we profiled its action on 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) E-2, PGD(2), and PGF(2). -13-COOH inhibits proinflammatory pathways in LPS-stimulated RAW264.7 macrophages more efficiently than -TOH. Profiling inflammation-related genes showed significant blocking of interleukin (Il)1 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 -13-COOH. Interestingly, -13-COOH acted independently from translocation of NFB subunit p65. ConclusionOur study sheds new light on the mode of action of -TOH on the inflammatory response in macrophages, which may be mediated in vivo at least in part by its metabolite -13-COOH. Our data show that -13-COOH is a potent anti-inflammatory molecule.