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

J. Biol. Chem., Vol. 282, Issue 37, 27155-27164, September 14, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/37/27155    most recent M704408200v1 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 Treede, I. Articles by Ehehalt, R. Search for Related Content PubMed PubMed Citation Articles by Treede, I. Articles by Ehehalt, R. Social Bookmarking                      What's this?

Anti-inflammatory Effects of Phosphatidylcholine^*

Irina Treede¹, Annika Braun, Richard Sparla, Mark Kühnel, Thomas Giese^¶, Jerrold R. Turner^||, Elsa Anes^**2, Hasan Kulaksiz, Joachim Füllekrug³, Wolfgang Stremmel, Gareth Griffiths, and Robert Ehehalt³⁴

From the Department of Gastroenterology, University Hospital Heidelberg, INF 345, Heidelberg 69120, Germany, the Cell Biology Program, European Molecular Biology Laboratory, Postfach 102209, Heidelberg 69117, Germany, the ^¶Institute of Immunology, University of Heidelberg, Im Neuenheimer Feld 305, Heidelberg 69120, Germany, the ^**Unidade dos Retrovirus e Infeccdoas Associades(URIA)-Molecular Pathogenesis Centre, Faculty of Pharmacy, University of Lisbon, av. das Forcas Armadas, Lisbon 1600-083, Portugal, and the ^||Department of Pathology, University of Chicago, MC-1089, 60637 Chicago, Illinois

We recently showed that mucus from patients with ulcerative colitis, a chronic inflammatory disorder of the colon, is characterized by a low level of phosphatidylcholine (PC) while clinical studies reveal that therapeutic addition of PC using slow release preparations is beneficial. The positive role of PC in this disease is still elusive. Here we tested the hypothesis that exogenous application of PC has anti-inflammatory properties using three model systems. First, human Caco-2 cells were treated with tumor necrosis factor- (TNF-) to induce a pro-inflammatory response via activation of NF-B. Second, latex bead phagosomes were analyzed for their ability to assemble actin in vitro, a process linked to pro-inflammatory signaling and correlating with the growth versus killing of mycobacteria in macrophages. The third system used was the rapid assembly of plasma membrane actin in macrophages in response to sphingosine 1-phosphate. TNF- induced a pro-inflammatory response in Caco-2 cells, including 1) assembly of plasma membrane actin; 2) activation of both MAPKs ERK and p38; 3) transport of NF-B subunits to the nucleus; and 4) subsequent up-regulation of the synthesis of pro-inflammatory gene products. Exogenous addition of most PCs tested significantly inhibited these processes. Other phospholipids like sphingomyelin or phosphatidylethanolamine showed no effects in these assays. PC also inhibited latex bead phagosome actin assembly, the killing of Mycobacterium tuberculosis in macrophages, and the sphingosine 1-phosphate-induced actin assembly in macrophages. TNF- induces the activation of signaling molecules and the reorganization of the actin cytoskeleton in human intestinal cells. Exogenous application of PC blocks pro-inflammatory signaling in Caco-2 cells, in phagosomes in vitro and facilitates intracellular survival of mycobacteria. We provide further evidence that actin assembly by membranes is part of the pro-inflammatory response. Collectively, these results provide a molecular foundation for the clinical studies showing a beneficial effect of PC therapy in ulcerative colitis.

Received for publication, May 29, 2007 , and in revised form, July 12, 2007.

^* 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.

¹ Supported by the Young Investigator Award of the Medical Faculty of Heidelberg.

² Supported by the Fundacio para a Ciencia ea Tecnologia (FCT) (Grant POCI/BIA-BCM/55327/2004) with co-participation of the Eu Fonds Europeans de Developpement Regional (FEDER) program POCI2010.

³ Supported by a grant from the Stiftung Nephrologie.

⁴ To whom correspondence should be addressed: Tel.: 49-6221-563-8715; Fax: 49-06221-565-398; E-mail: robert_ehehalt{at}med.uni-heidelberg.de.

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

This article has been cited by other articles:

				Mark. P. Kuehnel, V. Rybin, P. K. Anand, E. Anes, and G. Griffiths Lipids regulate P2X7-receptor-dependent actin assembly by phagosomes via ADP translocation and ATP synthesis in the phagosome lumen J. Cell Sci., February 15, 2009; 122(4): 499 - 504. [Abstract] [Full Text] [PDF]

				D. R. Gude, S. E. Alvarez, S. W. Paugh, P. Mitra, J. Yu, R. Griffiths, S. E. Barbour, S. Milstien, and S. Spiegel Apoptosis induces expression of sphingosine kinase 1 to release sphingosine-1-phosphate as a "come-and-get-me" signal FASEB J, August 1, 2008; 22(8): 2629 - 2638. [Abstract] [Full Text] [PDF]