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α‐Tocopherol long‐chain metabolite α‐13’‐COOH affects the inflammatory response of lipopolysaccharide‐activated murine RAW264.7 macrophages
Author(s) -
Wallert Maria,
Schmölz Lisa,
Koeberle Andreas,
Krauth Verena,
Glei Michael,
Galli Francesco,
Werz Oliver,
Birringer Marc,
Lorkowski Stefan
Publication year - 2015
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201400737
Subject(s) - nitric oxide , metabolite , chemistry , lipopolysaccharide , proinflammatory cytokine , inflammation , nitric oxide synthase , biochemistry , downregulation and upregulation , pharmacology , biology , endocrinology , immunology , gene , organic chemistry
Scope 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 semisynthetically‐derived α‐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 2α . α‐13′‐COOH inhibits proinflammatory 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.