S-adenosylmethionine (AdoMet) modulates endotoxin stimulated interleukin-10 production in monocytes.
IL-10 is produced by a large variety of cells including monocytes, macrophages, B and T lymphocytes, as well as natural killer cells and is an important suppressor for both immunoproliferative and inflammatory responses. IL-10 exerts antifibrotic effects in the liver, and decreased monocyte synthesis of IL-10 is well documented in alcoholic cirrhosis. Intracellular deficiency of S-adenosylmethionine (AdoMet) is a hallmark of toxin-induced liver injury. Although the administration of exogenous AdoMet attenuates this injury, the mechanisms of its actions are not fully established. This study was performed to investigate the effect of exogenous AdoMet on IL-10 production in LPS-stimulated RAW 264.7 cells, a murine macrophage cell line. Our results demonstrated that exogenous AdoMet administration enhanced both protein production and gene expression of IL-10 in RAW 264.7 cells. Ethionine, an inhibitor for methionine adenosyltransferases, inhibited LPS-stimulated IL-10 both at the protein and mRNA levels. Exogenous AdoMet increased the intracellular cAMP concentration as early as 3 h and continued for 24 h after AdoMet treatment; however, the inhibitors for both adenylyl cyclase and PKA did not significantly affect IL-10 production. On the basis of these results, we conclude that AdoMet administration may exert its anti-inflammatory and hepatoprotective effects, at least in part, by enhancing LPS-stimulated IL-10 production.
Department of Medicine, University of Louisville School of Medicine and Department of Veterans Affairs Medical Center, Louisville, Kentucky 40292, USA.
Zhenyuan
Z
Song
Shirish
S
Barve
Theresa
T
Chen
Wendy
W
Nelson
Silvia
S
Uriarte
Daniell
D
Hill
Craig
C
McClain
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D003515:Cycloleucine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005001:Ethionine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D000906:Antibodies; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D003515:Cycloleucine; D016753:Interleukin-10; D012436:S-Adenosylmethionine; D000242:Cyclic AMP; D005001:Ethionine