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PMID: 19594939 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

TNF-alpha-induced up-regulation of pro-inflammatory cytokines is reduced by phosphatidylcholine in intestinal epithelial cells.

BMC gastroenterology ·Vol. 9 ·2009-07-13 ·Pages 53

Treede I, Braun A, Jeliaskova P, Giese T, Füllekrug J, Griffiths G, Stremmel W, Ehehalt R

Abstract

Phosphatidylcholine (PC) is a major lipid of the gastrointestinal mucus layer. We recently showed that mucus from patients suffering from ulcerative colitis has low levels of PC. Clinical studies reveal that the therapeutic addition of PC to the colonic mucus using slow release preparations is beneficial. The positive role of PC in this disease is still unclear; however, we have recently shown that PC has an intrinsic anti-inflammatory property. It could be demonstrated that the exogenous application of PC inhibits membrane-dependent actin assembly and TNF-alpha-induced nuclear NF-kappaB activation. We investigate here in more detail the hypothesis that the exogenous application of PC has anti-inflammatory properties. PC species with different fatty acid side chains were applied to differentiated and non-differentiated Caco-2 cells treated with TNF-alpha to induce a pro-inflammatory response. We analysed TNF-alpha-induced NF-kappaB-activation via the transient expression of a NF-kappaB-luciferase reporter system. Pro-inflammatory gene transcription was detected with the help of a quantitative real time (RT)-PCR analysis. We assessed the binding of TNF-alpha to its receptor by FACS and analysed lipid rafts by isolating detergent resistant membranes (DRMs). The exogenous addition of all PC species tested significantly inhibited TNF-alpha-induced pro-inflammatory signalling. The expression levels of IL-8, ICAM-1, IP-10, MCP-1, TNF-alpha and MMP-1 were significantly reduced after PC pre-treatment for at least two hours. The effect was comparable to the inhibition of NF-kB by the NF-kB inhibitor SN 50 and was not due to a reduced binding of TNF-alpha to its receptor or a decreased surface expression of TNF-alpha receptors. PC was also effective when applied to the apical side of polarised Caco-2 cultures if cells were stimulated from the basolateral side. PC treatment changed the compartmentation of the TNF-alpha-receptors 1 and 2 to DRMs. PC induces a prolonged inhibition of TNF-alpha-induced pro-inflammatory signalling. This inhibition may be caused by a shift of the TNF-alpha receptors at the surface to lipid rafts. Our results may offer a potential molecular explanation for the positive role of PC seen in clinical studies for the treatment of ulcerative colitis.

MeSH Terms
Cell Line Chemokine CCL2/metabolism Cytokines/metabolism Humans Intercellular Adhesion Molecule-1/metabolism Interleukin-8/metabolism Intestinal Mucosa/cytology,drug effects,metabolism Matrix Metalloproteinase 1/metabolism NF-kappa B/metabolism Phosphatidylcholines/pharmacology Receptors, Tumor Necrosis Factor/metabolism Tumor Necrosis Factor-alpha/metabolism,pharmacology Up-Regulation/drug effects
Chemicals
CCL2 protein, human Chemokine CCL2 Cytokines Interleukin-8 NF-kappa B Phosphatidylcholines Receptors, Tumor Necrosis Factor Tumor Necrosis Factor-alpha Intercellular Adhesion Molecule-1 Matrix Metalloproteinase 1
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Treede Irina
Department of Gastroenterology, University of Heidelberg, Heidelberg, Germany. [email protected]
Braun Annika
Jeliaskova Petia
Giese Thomas
Füllekrug Joachim
Griffiths Gareth
Stremmel Wolfgang
Ehehalt Robert
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Article Info
Journal
BMC gastroenterology
Abbr.
BMC Gastroenterol
ISSN
1471-230X
DOI
10.1186/1471-230X-9-53
Email
[email protected]
Published
2009-07-13
Epub
2009-00-13
Pages
53
Language
English
Region
England
NLM ID
100968547
PMCID
PMC2714528
Subset
IM
External Links
PubMed source DOI: 10.1186/1471-230X-9-53 PMC Full Text View journal details
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