Down-regulation by troglitazone of hepatic tumor necrosis factor-α and interleukin-6 mRNA expression in a murine model of non-insulin-dependent diabetes

摘要: Abstract Troglitazone, a novel thiazolidinedione drug used to treat non-insulin-dependent diabetes mellitus, is selective ligand for the peroxisome proliferator-activated receptor-γ (PPARγ). Recent results indicate that PPARγ activation by thiazolidinediones regulates adipose tissue- and monocyte/peritoneal macrophage-derived cytokine expression in vitro . We evaluated whether troglitazone may also negatively regulate liver, which harbors majority of body’s resident macrophages but only weakly expresses PPARγ. Lean C57BL6 mice genetically obese KKA y were chronically treated with (100 mg/kg/day 2 weeks). At end treatment, hepatic tumor necrosis factor (TNF)-α interleukin (IL)-6 mRNA was quantitatively determined kinetic polymerase chain reaction both under basal conditions after stimulation lipopolysaccharide (LPS). Both untreated lean exhibited low levels baseline TNF-α IL-6 responded dramatic increase transcripts protein following challenge LPS. Similar effects on white tissue, not down-regulated IL-6, greatly attenuated inducing The extent this inhibitory effect higher than reflected markedly expression. These data demonstrate chronic administration associated responsiveness towards inducers production. possible biological consequences these effects, however, have yet been assessed.