Abstract

Nuclear factor-?B (NF-?B) is a redox-sensitive factor responsible for the transcriptional activation of cytokine-encoding genes. In this study, we show that 3,3,5-triiodothyronine (T3) administration to rats activates hepatic NF-?B, as assessed by electrophoretic mobility shift assay. This response coincides with the onset of calorigenesis and enhancement in hepatic respiration, and is suppressed by the antioxidants ?-tocopherol and N-acetylcysteine or by the Kupffer cell inactivator gadolinium chloride. Livers from hyperthyroid rats with enhanced NF-?B DNA-binding activity show induced mRNA expression of the NF-?B-responsive genes for tumor necrosis factor-? (TNF-?) and interleukin- (IL-) 10, as evidenced by reverse transcription-polymerase chain reaction assay, which is correlated with increases in the serum levels of the cytokines. T 3 also increased the hepatic levels of mRNA for IL-1? and those of IL-1? in serum, with a time profile closely related to that of TNF-?. It is concluded that T3-induced oxidative stress enhances the DNA-binding activity of NF-?B and the NF-?B-dependent expression of TNF-? and IL-10 genes. © 2003 Elsevier Inc.