Lipoic acid stimulates cAMP production via the EP2 and EP4 prostanoid receptors and inhibits IFN gamma synthesis and cellular cytotoxicity in NK cells

Sonemany Salinthone, Robynn V. Schillace, Gail H. Marracci, Dennis N. Bourdette, Daniel W. Carr

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

The antioxidant lipoic acid (LA) treats and prevents the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). In an effort to understand the therapeutic potential of LA in MS, we sought to define the cellular mechanisms that mediate the effects of LA on human natural killer (NK) cells, which are important in innate immunity as the first line of defense against invading pathogens and tumor cells. We discovered that LA stimulates cAMP production in NK cells in a dose-dependent manner. Studies using pharmacological inhibitors and receptor transfection experiments indicate that LA stimulates cAMP production via activation of the EP2 and EP4 prostanoid receptors and adenylyl cyclase. In addition, LA suppressed interleukin (IL)-12/IL-18 induced IFNγ secretion and cytotoxicity in NK cells. These novel findings suggest that LA may inhibit NK cell function via the cAMP signaling pathway.

Original languageEnglish (US)
Pages (from-to)46-55
Number of pages10
JournalJournal of Neuroimmunology
Volume199
Issue number1-2
DOIs
StatePublished - Aug 13 2008

Keywords

  • IFNγ
  • Multiple sclerosis
  • Natural killer cells
  • Thioctic acid
  • cAMP

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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