HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sancho, R. Articles by Muñoz, E. Search for Related Content PubMed PubMed Citation Articles by Sancho, R. Articles by Muñoz, E.

Immunosuppressive Activity of Endovanilloids: N-Arachidonoyl-Dopamine Inhibits Activation of the NF-B, NFAT, and Activator Protein 1 Signaling Pathways ¹

Rocío Sancho^*, Antonio Macho^*, Laureano de La Vega^*, Marco A. Calzado^*, Bernd L. Fiebich^,, Giovanni Appendino and Eduardo Muñoz^2,*

^* Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Facultad de Medicina, Cordoba, Spain; Neurochemistry Research Group, Department of Psychiatry, University of Freiburg Medical School, Germany; VivaCell Biotechnology, Denzlingen, Germany; and Università degli Studi del Piemonte Orientale, Dipartimento de Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Novara, Italy

Endogenous N-acyl dopamines such as N-arachidonoyldopamine (NADA) and N-oleoyldopamine have been recently identified as a new class of brain neurotransmitters sharing endocannabinoid and endovanilloid biological activities. As endocannabinoids show immunomodulatory activity, and T cells play a key role in the onset of several diseases that affect the CNS, we have evaluated the immunosuppressive activity of NADA and N-oleoyldopamine in human T cells, discovering that both compounds are potent inhibitors of early and late events in TCR-mediated T cell activation. Moreover, we found that NADA specifically inhibited both IL-2 and TNF- gene transcription in stimulated Jurkat T cells. To further characterize the inhibitory mechanisms of NADA at the transcriptional level, we examined the DNA binding and transcriptional activities of NF-B, NF-AT, and AP-1 transcription factors in Jurkat cells. We found that NADA inhibited NF-B-dependent transcriptional activity without affecting either degradation of the cytoplasmic NF-B inhibitory protein, IB, or DNA binding activity. However, phosphorylation of the p65/RelA subunit was clearly inhibited by NADA in stimulated cells. In addition, NADA inhibited both binding to DNA and the transcriptional activity of NF-AT and AP-1, as expected from the inhibition of NF-AT1 dephosphorylation and c-Jun N-terminal kinase activation in stimulated T cells. Finally, overexpression of a constitutively active form of calcineurin demonstrated that this phosphatase may represent one of the main targets of NADA. These findings provide new mechanistic insights into the anti-inflammatory activities of NADA and highlight their potential to design novel therapeutic strategies to manage inflammatory diseases.

This article has been cited by other articles:

				M. Bari, P. Spagnuolo, F. Fezza, S. Oddi, N. Pasquariello, A. Finazzi-Agro, and M. Maccarrone Effect of Lipid Rafts on Cb2 Receptor Signaling and 2-Arachidonoyl-Glycerol Metabolism in Human Immune Cells J. Immunol., October 15, 2006; 177(8): 4971 - 4980. [Abstract] [Full Text] [PDF]

				C. Navarrete, R. Sancho, F. J. Caballero, F. Pollastro, B. L. Fiebich, O. Sterner, G. Appendino, and E. Munoz Basiliolides, a Class of Tetracyclic C19 Dilactones from Thapsia garganica, Release Ca2+ from the Endoplasmic Reticulum and Regulate the Activity of the Transcription Factors Nuclear Factor of Activated T Cells, Nuclear Factor-{kappa}B, and Activator Protein 1 in T Lymphocytes J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 422 - 430. [Abstract] [Full Text] [PDF]

				N. Marquez, L. De Petrocellis, F. J. Caballero, A. Macho, A. Schiano-Moriello, A. Minassi, G. Appendino, E. Munoz, and V. Di Marzo Iodinated N-Acylvanillamines: Potential "Multiple-Target" Anti-Inflammatory Agents Acting via the Inhibition of T-Cell Activation and Antagonism at Vanilloid TRPV1 Channels Mol. Pharmacol., April 1, 2006; 69(4): 1373 - 1382. [Abstract] [Full Text] [PDF]

				S. M. Huang and J. M. Walker Enhancement of Spontaneous and Heat-Evoked Activity in Spinal Nociceptive Neurons by the Endovanilloid/Endocannabinoid N-Arachidonoyldopamine (NADA) J Neurophysiol, February 1, 2006; 95(2): 1207 - 1212. [Abstract] [Full Text] [PDF]

				R. Sancho, L. de la Vega, A. Macho, G. Appendino, V. Di Marzo, and E. Munoz Mechanisms of HIV-1 Inhibition by the Lipid Mediator N-Arachidonoyldopamine J. Immunol., September 15, 2005; 175(6): 3990 - 3999. [Abstract] [Full Text] [PDF]