Modulation of endotoxin stimulated interleukin-6 production in monocytes and Kupffer cells by S-adenosylmethionine (SAMe).
Interleukin-6 (IL-6) is a multifunctional cytokine having primarily anti-apoptotic and anti-inflammatory effects. Recent reports have documented that IL-6 plays a key role in liver regeneration. Intracellular deficiency of S-adenosylmethionine (SAMe) is a hallmark of toxin-induced liver injury. Although the administration of exogenous SAMe attenuates liver injury, its mechanisms of action are not fully understood. Here we investigated the effects of exogenous SAMe on IL-6 production in monocytes and Kupffer cells. RAW 264.7 cells, a murine monocyte cell line, and isolated rat Kupffer cells were stimulated with lipopolysaccharide (LPS) in the absence or presence of exogenous SAMe. IL-6 production was assayed by ELISA and intracellular SAMe concentrations were measured by HPLC. We have found that exogenous SAMe administration enhanced both IL-6 protein production and gene expression in LPS-stimulated monocytes and Kupffer cells. Cycloleucine (CL), an inhibitor for extrahepatic methionine adenosyltransferases (MAT), inhibited LPS-stimulated IL-6 production. The enhancement of LPS-stimulated IL-6 production by SAMe was inhibited by ZM241385, a specific antagonist of adenosine (A2) receptor. Our results demonstrate that SAMe administration may exert its anti-inflammatory and hepatoprotective effects, at least in part, by enhancing LPS-stimulated IL-6 production.
Song
Zhenyuan
Z
Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Chen
Theresa
T
Deaciuc
Ion V
IV
Uriarte
Silvia
S
Hill
Daniell
D
Barve
Shirish
S
McClain
Craig J
CJ
D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D003515:Cycloleucine / Q000378:metabolism; D015536:Down-Regulation; D005978:Glutathione / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism*; D008070:Lipopolysaccharides; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism*
D015850:Interleukin-6; D008070:Lipopolysaccharides; D003515:Cycloleucine; D012436:S-Adenosylmethionine; D005978:Glutathione; D000111:Acetylcysteine