Document Detail

Role for PPARgamma in IL-2 inhibition in T cells by Echinacea-derived undeca-2E-ene-8,10-diynoic acid isobutylamide.
MedLine Citation:
PMID:  19712756     Owner:  NLM     Status:  MEDLINE    
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.
Kevin Spelman; Katrina Iiams-Hauser; Nadja B Cech; Ethan Will Taylor; Nicholas Smirnoff; Cynthia A Wenner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-08-25
Journal Detail:
Title:  International immunopharmacology     Volume:  9     ISSN:  1878-1705     ISO Abbreviation:  Int. Immunopharmacol.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-23     Completed Date:  2010-01-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100965259     Medline TA:  Int Immunopharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1260-4     Citation Subset:  IM    
University of North Carolina Greensboro, Department of Chemistry and Biochemistry, P.O. Box 26170, Greensboro, NC 27405, USA.
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MeSH Terms
3T3-L1 Cells
Benzamides / pharmacology
Cell Differentiation / drug effects,  physiology
Cell Survival / drug effects
Drug Interactions
Echinacea / metabolism
Interleukin-2 / antagonists & inhibitors*,  secretion
Jurkat Cells
PPAR gamma / antagonists & inhibitors,  physiology*
Polyunsaturated Alkamides / pharmacology*
Pyridines / pharmacology
Reg. No./Substance:
0/Benzamides; 0/Interleukin-2; 0/PPAR gamma; 0/Polyunsaturated Alkamides; 0/Pyridines; 0/T 0070907

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