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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Suppression of TNF-α production by S-adenosylmethionine in human mononuclear leukocytes is not mediated by polyamines

Jingling Yu
  • University of Hohenheim (140e), Department of Physiology of Nutrition and Gender Research, D-70599 Stuttgart, Germany
/ Senja Sauter
  • University of Hohenheim (140e), Department of Physiology of Nutrition and Gender Research, D-70599 Stuttgart, Germany
/ Alexandr Parlesak
  • University of Hohenheim (140e), Department of Physiology of Nutrition and Gender Research, D-70599 Stuttgart, Germany
Published Online: 2006-11-28 | DOI: https://doi.org/10.1515/BC.2006.202


Endotoxin-induced cytokine production is an important mechanism in the development of several types of liver damage. Methionine, some of its precursors and metabolites were reported to have protective effects against such injury. The aim of this study was to investigate whether methionine, its precursors or metabolites [phosphatidylcholine, choline, betaine, S-adenosylmethionine (SAM)] have a modulating effect on tumor necrosis factor α (TNF-α) production by endotoxin-stimulated human mononuclear leukocytes and whether SAM-dependent polyamines (spermidine, spermine) are mediators of SAM-induced inhibition of TNF-α synthesis. Methionine and betaine had a moderate stimulatory effect on TNF-α production, whereas phosphatidylcholine (ID50 5.4 mM), SAM (ID50 131 μM), spermidine (ID50 4.5 μM) and spermine (ID50 3.9 μM) had a predominantly inhibitory effect. Putrescine did not alter TNF-α release. Inhibitors of polyamine synthesis that blocked either putrescine (difluoromethylornithine) or spermine (CGP48664A) production did not affect TNF-α synthesis. Endotoxin stimulation of leukocytes did not alter the intracellular levels of polyamines. In addition, supplementation with SAM did not change the intracellular concentration of either polyamine measured. We conclude that phosphatidylcholine-induced immunosuppression is not caused by methionine and polyamines are not involved in SAM-induced inhibition of TNF-α production. The limitation of TNF-α release by spermidine is specific and is not due to its conversion into spermine.

Keywords: inflammation; lipopolysaccharide; methionine; putrescine; spermidine; spermine

Corresponding author

Received: March 21, 2006

Accepted: August 22, 2006

Published Online: 2006-11-28

Published in Print: 2006-12-01

Citation Information: Biological Chemistry. Volume 387, Issue 12, Pages 1619–1627, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2006.202, November 2006

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