Maria Wallert1,2, Lisa Schmölz1,2, Andreas Koeberle3, Verena Krauth3, Michael Glei2,3,4, Francesco Galli5, Oliver Werz2,3, Marc Birringer6, Stefan Lorkowski1,2. 1. Department of Nutritional Biochemistry and Physiology, Institute of Nutrition, Friedrich Schiller University Jena, Jena, Germany. 2. Competence Cluster of Nutrition and Cardiovascular Health (nutriCARD), Friedrich Schiller University Jena, Jena, Germany. 3. Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Jena, Germany. 4. Department of Nutrition Toxicology, Institute of Nutrition, Friedrich Schiller University Jena, Jena, Germany. 5. Department of Pharmaceutical Sciences, Laboratory of Nutrition and Clinical Biochemistry, University of Perugia, Perugia, Italy. 6. Department of Nutritional, Food and Consumer Studies, HS Fulda - University of Applied Sciences, Fulda, Germany.
Abstract
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) E2 , PGD2 , and PGF2α. 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.
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) E2 , PGD2 , and PGF2α. 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.
Authors: Martin Schubert; Stefan Kluge; Lisa Schmölz; Maria Wallert; Francesco Galli; Marc Birringer; Stefan Lorkowski Journal: Antioxidants (Basel) Date: 2018-01-12
Authors: Anke Katharina Müller; Franziska Albrecht; Carsten Rohrer; Andreas Koeberle; Oliver Werz; Wiebke Schlörmann; Michael Glei; Stefan Lorkowski; Maria Wallert Journal: Nutrients Date: 2021-12-11 Impact factor: 5.717