title: Modulation of endotoxin stimulated interleukin-6 production in monocytes and Kupffer cells by S-adenosylmethionine (SAMe).
abstract: 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.
authors.affiliation: Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA.
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Song
authors.forename: Theresa
authors.initials: T
authors.lastname: Chen
authors.forename: Ion V
authors.initials: IV
authors.lastname: Deaciuc
authors.forename: Silvia
authors.initials: S
authors.lastname: Uriarte
authors.forename: Daniell
authors.initials: D
authors.lastname: Hill
authors.forename: Shirish
authors.initials: S
authors.lastname: Barve
authors.forename: Craig J
authors.initials: CJ
authors.lastname: McClain
mesh_terms: 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*
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D003515:Cycloleucine; D012436:S-Adenosylmethionine; D005978:Glutathione; D000111:Acetylcysteine