Role for PPARgamma in IL-2 inhibition in T cells by Echinacea-derived undeca-2E-ene-8,10-diynoic acid isobutylamide.
Certain fatty acid amides from Echinacea spp. have demonstrated moderate to high cannabinoid activity. As a result, CB2 activation is currently hypothesized to be the basis of activity for immunomodulation by Echinacea spp. PPARgamma, an orphan nuclear receptor and lipid sensor, is known to inhibit IL-2 production and be activated by fatty acid derivatives such as the endocannabinoids. In these investigations, we demonstrate that undeca-2E-ene-8,10-diynoic acid, an Echinacea angustifolia-derived alkylamide lacking affinity for the CB2 receptor, inhibits IL-2 secretion in Jurkat T cells through PPARgamma activity at low micromolar concentrations (330 ng/mL). The IL-2 inhibition is reversed by the addition of the selective PPARgamma antagonist T0070907. Additionally, we show that that undeca-2-ene-8,10-diynoic acid stimulates 3T3-L1 differentiation, a process dependent on PPARgamma activity. These experiments demonstrate that PPARgamma is involved in T cell IL-2 inhibition by undeca-2-ene-8,10-diynoic acid and suggest that cytokine modulation by the alkylamides is due to polyvalent activity.
Spelman
Kevin
K
University of North Carolina Greensboro, Department of Chemistry and Biochemistry, P.O. Box 26170, Greensboro, NC 27405, USA.
Iiams-Hauser
Katrina
K
Cech
Nadja B
NB
Taylor
Ethan Will
EW
Smirnoff
Nicholas
N
Wenner
Cynthia A
CA
D041721:3T3-L1 Cells; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D020900:Echinacea / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019169:Jurkat Cells; D051379:Mice; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000502:physiology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology
D001549:Benzamides; D007376:Interleukin-2; D047495:PPAR gamma; D053284:Polyunsaturated Alkamides; D011725:Pyridines; C458508:T 0070907