α-Tocopherol (vitamin E) stimulates cyclic AMP production in human peripheral mononuclear cells and alters immune function

Mol Immunol. 2013 Mar;53(3):173-8. doi: 10.1016/j.molimm.2012.08.005. Epub 2012 Sep 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology
  • Cells, Cultured
  • Chemokine CCL5 / biosynthesis
  • Cyclic AMP / biosynthesis*
  • Dose-Response Relationship, Drug
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / pharmacology
  • Inflammation Mediators / metabolism
  • Interleukin-17 / biosynthesis
  • Interleukin-2 / biosynthesis
  • Interleukin-8 / biosynthesis
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism*
  • Receptors, Prostaglandin E, EP2 Subtype / metabolism
  • Receptors, Prostaglandin E, EP4 Subtype / metabolism
  • Signal Transduction / drug effects
  • alpha-Tocopherol / administration & dosage
  • alpha-Tocopherol / pharmacology*

Substances

  • Antioxidants
  • CCL5 protein, human
  • CXCL8 protein, human
  • Chemokine CCL5
  • IL2 protein, human
  • Immunologic Factors
  • Inflammation Mediators
  • Interleukin-17
  • Interleukin-2
  • Interleukin-8
  • PTGER2 protein, human
  • PTGER4 protein, human
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype
  • Cyclic AMP
  • Adenylyl Cyclases
  • alpha-Tocopherol