TY - JOUR
T1 - Lipoic acid stimulates cAMP production via the EP2 and EP4 prostanoid receptors and inhibits IFN gamma synthesis and cellular cytotoxicity in NK cells
AU - Salinthone, Sonemany
AU - Schillace, Robynn V.
AU - Marracci, Gail H.
AU - Bourdette, Dennis N.
AU - Carr, Daniel W.
N1 - Funding Information:
We would like to thank Sarah Fiedler and Casey Miller for helpful critique of the manuscript. This research was supported by the Department of Veterans Affairs Biomedical Laboratory Research & Development Service (D.W.C. and D.N.B.), NIH Grant P50AT00066-01 (D.N.B.), and the Nancy Davis Center Without Walls (D.N.B.).
PY - 2008/8/13
Y1 - 2008/8/13
N2 - 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.
AB - 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.
KW - IFNγ
KW - Multiple sclerosis
KW - Natural killer cells
KW - Thioctic acid
KW - cAMP
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U2 - 10.1016/j.jneuroim.2008.05.003
DO - 10.1016/j.jneuroim.2008.05.003
M3 - Article
C2 - 18562016
AN - SCOPUS:47549093704
SN - 0165-5728
VL - 199
SP - 46
EP - 55
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -