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PMID: 17636253 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Anti-inflammatory effects of phosphatidylcholine.

The Journal of biological chemistry ·Vol. 282 ·No. 37 ·2007-09-14 ·Pages 27155-27164

Treede I, Braun A, Sparla R, Kühnel M, Giese T, Turner JR, Anes E, Kulaksiz H, Füllekrug J, Stremmel W, Griffiths G, Ehehalt R

Abstract

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-alpha (TNF-alpha) to induce a pro-inflammatory response via activation of NF-kappaB. 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-alpha 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-kappaB 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-alpha 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.

MeSH Terms
Actins/chemistry Anti-Inflammatory Agents/pharmacology Caco-2 Cells Cell Polarity Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors,metabolism Humans Macrophages/drug effects,microbiology NF-kappa B/metabolism Phagosomes/metabolism Phosphatidylcholines/pharmacokinetics,pharmacology Tumor Necrosis Factor-alpha/antagonists & inhibitors p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors,metabolism
Chemicals
Actins Anti-Inflammatory Agents NF-kappa B Phosphatidylcholines Tumor Necrosis Factor-alpha Extracellular Signal-Regulated MAP Kinases p38 Mitogen-Activated Protein Kinases
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Treede Irina
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.
Braun Annika
Department of Gastroenterology, University Hospital Heidelberg, INF 345, Heidelberg 69120, Germany, the.
Sparla Richard
Department of Gastroenterology, University Hospital Heidelberg, INF 345, Heidelberg 69120, Germany, the.
Kühnel Mark
Cell Biology Program, European Molecular Biology Laboratory, Postfach 102209, Heidelberg 69117, Germany, the.
Giese Thomas
Institute of Immunology, University of Heidelberg, Im Neuenheimer Feld 305, Heidelberg 69120, Germany, the.
Turner Jerrold R
Department of Pathology, University of Chicago, MC-1089, 60637 Chicago, Illinois.
Anes Elsa
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.
Kulaksiz Hasan
Department of Gastroenterology, University Hospital Heidelberg, INF 345, Heidelberg 69120, Germany, the.
Füllekrug Joachim
Department of Gastroenterology, University Hospital Heidelberg, INF 345, Heidelberg 69120, Germany, the.
Stremmel Wolfgang
Department of Gastroenterology, University Hospital Heidelberg, INF 345, Heidelberg 69120, Germany, the.
Griffiths Gareth
Cell Biology Program, European Molecular Biology Laboratory, Postfach 102209, Heidelberg 69117, Germany, the.
Ehehalt Robert
Department of Gastroenterology, University Hospital Heidelberg, INF 345, Heidelberg 69120, Germany, the. Electronic address: [email protected].
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M704408200
Email
[email protected]
Published
2007-09-14
Epub
2007-00-18
Pages
27155-27164
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2693065
Subset
IM
Grants
NIDDK NIH HHS · R01 DK061931 · United States
NIDDK NIH HHS · R01 DK061931-07 · United States
NIDDK NIH HHS · R01 DK068271 · United States
NIDDK NIH HHS · R01 DK068271-03 · United States
External Links
PubMed source DOI: 10.1074/jbc.M704408200 PMC Full Text View journal details
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