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

J. Biol. Chem., Vol. 280, Issue 14, 14293-14301, April 8, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/14/14293    most recent M410000200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Zeyda, M. Articles by Stulnig, T. M. Search for Related Content PubMed PubMed Citation Articles by Zeyda, M. Articles by Stulnig, T. M. Social Bookmarking                      What's this?

Polyunsaturated Fatty Acids Block Dendritic Cell Activation and Function Independently of NF-B Activation^*

Maximilian Zeyda, Marcus D. Säemann, Karl M. Stuhlmeier¶, Daniel G. Mascher||, Peter N. Nowotny, Gerhard J. Zlabinger**, Werner Waldhäusl, and Thomas M. Stulnig

From the Clinical Divisions of Endocrinology and Metabolism and Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria, the ^¶Ludwig Boltzmann Institute for Rheumatology and Balneology, Kurbadstrasse 10, POB 78, A-1107 Vienna, Austria, the ^||Pharm-analyt Laboratory GmbH, Ferdinand-Pichler-Gasse 2, A-2500 Baden, Austria, the ^**Institute of Immunology, Medical University of Vienna, Borschkegasse 8A, A-1090 Vienna, Austria, and the CeMM Center of Molecular Medicine of the Austrian Academy of Sciences, Schopenhauerstrasse 40, A-7780 Vienna, Austria

Polyunsaturated fatty acids (PUFAs) modulate immune responses leading to clinically significant beneficial effects in a variety of inflammatory disorders. PUFA effects on T cells have been extensively studied, but their influence on human dendritic cells (DCs), which are the most potent antigen-presenting cells and play a key role in initiating immune responses, has not been elucidated so far. Here we show that PUFAs of the n-3 and n-6 series (arachidonic and eicosapentaenoic acid) affect human monocyte-derived DC differentiation and inhibit their activation by LPS, resulting in altered DC surface molecule expression and diminished cytokine secretion. Furthermore, the potency to stimulate T cells was markedly inhibited in PUFA-treated DCs. The PUFA-mediated block in LPS-induced DC activation is reflected by diminished TNF-, IL-12p40, CD40, and COX-2 mRNA levels. Strikingly, typical LPS-induced signaling events such as degradation of IB and activation of NF-B were not affected by PUFAs, even though DC membrane lipid composition was markedly altered. Arachidonic and eicosapentaenoic acid both altered DC prostaglandin production, but inhibitors of cyclooxygenases and lipoxygenases did not abolish PUFA effects, indicating that the observed PUFA actions on DCs were independent of autoregulation via eicosanoids. These data demonstrate a unique interference with DC activation and function that could significantly contribute to the well known anti-inflammatory effects of PUFAs.

Received for publication, August 31, 2004 , and in revised form, January 27, 2005.

^* This work was supported by the Austrian Science Fund (P16788-B13 (to T. M. S.) and P14874-B08 (to G. J. Z.)) and CeMM, Center of Molecular Medicine, a basic research institute within the Austrian Academy of Sciences, Vienna, Austria. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Clin. Div. of Endocrinology and Metabolism, Dept. of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18–20, A-1090 Vienna, Austria. Tel.: 43-1-40400-4368; Fax: 43-1-40400-7790; E-mail: thomas.stulnig{at}meduniwien.ac.at.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. Zapata-Gonzalez, F. Rueda, J. Petriz, P. Domingo, F. Villarroya, J. Diaz-Delfin, M. A. de Madariaga, and J. C. Domingo Human dendritic cell activities are modulated by the omega-3 fatty acid, docosahexaenoic acid, mainly through PPAR{gamma}:RXR heterodimers: comparison with other polyunsaturated fatty acids J. Leukoc. Biol., October 1, 2008; 84(4): 1172 - 1182. [Abstract] [Full Text] [PDF]

				E. K. Vassiliou, O. M. Kesler, J. H. Tadros, and D. Ganea Bone Marrow-Derived Dendritic Cells Generated in the Presence of Resolvin E1 Induce Apoptosis of Activated CD4+ T Cells J. Immunol., October 1, 2008; 181(7): 4534 - 4544. [Abstract] [Full Text] [PDF]

				B. Fontaine-Bisson, T. M. Wolever, J.-L. Chiasson, R. Rabasa-Lhoret, P. Maheux, R. G Josse, L. A Leiter, N W. Rodger, E. A Ryan, P. W Connelly, et al. Genetic polymorphisms of tumor necrosis factor-{alpha} modify the association between dietary polyunsaturated fatty acids and fasting HDL-cholesterol and apo A-I concentrations Am. J. Clinical Nutrition, September 1, 2007; 86(3): 768 - 774. [Abstract] [Full Text] [PDF]

				R. Geyeregger, M. Zeyda, W. Bauer, E. Kriehuber, M. D. Saemann, G. J. Zlabinger, D. Maurer, and T. M. Stulnig Liver X receptors regulate dendritic cell phenotype and function through blocked induction of the actin-bundling protein fascin Blood, May 15, 2007; 109(10): 4288 - 4295. [Abstract] [Full Text] [PDF]

				C. L. Butts, S. A. Shukair, K. M. Duncan, E. Bowers, C. Horn, E. Belyavskaya, L. Tonelli, and E. M. Sternberg Progesterone inhibits mature rat dendritic cells in a receptor-mediated fashion Int. Immunol., March 1, 2007; 19(3): 287 - 296. [Abstract] [Full Text] [PDF]

				S. R. Shaikh and M. Edidin Immunosuppressive effects of polyunsaturated fatty acids on antigen presentation by human leukocyte antigen class I molecules J. Lipid Res., January 1, 2007; 48(1): 127 - 138. [Abstract] [Full Text] [PDF]

				R. S. Chapkin, L. A. Davidson, L. Ly, B. R. Weeks, J. R. Lupton, and D. N. McMurray Immunomodulatory Effects of (n-3) Fatty Acids: Putative Link to Inflammation and Colon Cancer J. Nutr., January 1, 2007; 137(1): 200S - 204S. [Abstract] [Full Text] [PDF]

				S. R. Shaikh and M. Edidin Polyunsaturated fatty acids, membrane organization, T cells, and antigen presentation Am. J. Clinical Nutrition, December 1, 2006; 84(6): 1277 - 1289. [Abstract] [Full Text] [PDF]

				P. A. Bedford, V. Todorovic, E. D. A. Westcott, A. C. J. Windsor, N. R. English, H. O. Al-Hassi, K. S. Raju, S. Mills, and S. C. Knight Adipose tissue of human omentum is a major source of dendritic cells, which lose MHC Class II and stimulatory function in Crohn's disease J. Leukoc. Biol., September 1, 2006; 80(3): 546 - 554. [Abstract] [Full Text] [PDF]

				C. E. Loscher, E. Draper, O. Leavy, D. Kelleher, K. H. G. Mills, and H. M. Roche Conjugated Linoleic Acid Suppresses NF-{kappa}B Activation and IL-12 Production in Dendritic Cells through ERK-Mediated IL-10 Induction J. Immunol., October 15, 2005; 175(8): 4990 - 4998. [Abstract] [Full Text] [PDF]