Role for PPARgamma in IL-2 inhibition in T cells by Echinacea-derived undeca-2E-ene-8,10-diynoic acid isobutylamide

• Published in: International immunopharmacology 2009-10, Vol.9 (11), p.1260
• Main Authors: Spelman, Kevin, Iiams-Hauser, Katrina, Cech, Nadja B, Taylor, Ethan Will, Smirnoff, Nicholas, Wenner, Cynthia A
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells; Animals; Benzamides - pharmacology; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Survival - drug effects; Drug Interactions; Echinacea - metabolism; Humans; Interleukin-2 - antagonists & inhibitors; Interleukin-2 - secretion; Jurkat Cells; Mice; Polyunsaturated Alkamides - pharmacology; PPAR gamma - antagonists & inhibitors; PPAR gamma - physiology; Pyridines - pharmacology
• ISSN: 1878-1705
• DOI: 10.1016/j.intimp.2009.08.009

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.