Suppression of TNF-α production by S-adenosylmethionine in human mononuclear leukocytes is not mediated by polyamines
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Suppression of TNF-α production by S-adenosylmethionine in human mononuclear leukocytes is not mediated by polyamines. / Yu, Jingling; Sauter, Senja; Parlesak, Alexandr.
I: Biological Chemistry, Bind 387, Nr. 12, 2006, s. 1619-1627.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Suppression of TNF-α production by S-adenosylmethionine in human mononuclear leukocytes is not mediated by polyamines
AU - Yu, Jingling
AU - Sauter, Senja
AU - Parlesak, Alexandr
N1 - (Ekstern)
PY - 2006
Y1 - 2006
N2 - 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 μM), 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.
AB - 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 μM), 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.
KW - Faculty of Science
KW - Inflammation
KW - Lipopolysaccharide
KW - Methionine
KW - Putrescine
KW - Spermidine
KW - Spermine
U2 - 10.1515/BC.2006.202
DO - 10.1515/BC.2006.202
M3 - Journal article
VL - 387
SP - 1619
EP - 1627
JO - Biological Chemistry Hoppe-Seyler
JF - Biological Chemistry Hoppe-Seyler
SN - 1431-6730
IS - 12
ER -
ID: 317460307