title: α-Tocopherol (vitamin E) stimulates cyclic AMP production in human peripheral mononuclear cells and alters immune function.
abstract: α-Tocopherol, the most biologically active member of the vitamin E family of fat soluble compounds, exhibits both antioxidant and anti-inflammatory properties. However, its mechanisms of action are not fully understood. Here, we show that, unlike other antioxidants, α-tocopherol stimulates the production of cyclic adenosine monophosphate (cAMP). Inhibitor studies demonstrate that the prostaglandin EP2 and EP4 receptors and adenylyl cyclases mediate the effects of α-tocopherol on cAMP production. Additionally, we show that α-tocopherol attenuates pro-inflammatory cytokine and chemokine production. This study provides novel evidence that α-tocopherol stimulates cAMP signaling, suggesting a mechanism of action for the immunomodulatory effects of vitamin E.
authors.affiliation: Department of Veterans Affairs Medical Center, VA Medical Center, Portland, OR 97239, USA.
authors.forename: Sonemany
authors.initials: S
authors.lastname: Salinthone
authors.forename: Amelia R
authors.initials: AR
authors.lastname: Kerns
authors.forename: Vivian
authors.initials: V
authors.lastname: Tsang
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Carr
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis; D000242:Cyclic AMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000378:metabolism; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; C483024:CCL5 protein, human; C508606:CXCL8 protein, human; D018946:Chemokine CCL5; C508594:IL2 protein, human; D007155:Immunologic Factors; D018836:Inflammation Mediators; D020381:Interleukin-17; D007376:Interleukin-2; D016209:Interleukin-8; C545644:PTGER2 protein, human; C545650:PTGER4 protein, human; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D024502:alpha-Tocopherol