Thyroid hormone-induced oxidative stress triggers nuclear factor-κB activation and cytokine gene expression in rat liver

Nuclear factor-κB (NF-κB) 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-κB, 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 α-tocopherol and N-acetylcysteine or by the Kupffer cell inactivator gadolinium chloride. Livers from hyperthyroid rats with enhanced NF-κB DNA-binding activity show induced mRNA expression of the NF-κB-responsive genes for tumor necrosis factor-α (TNF-α) 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. T3 also increased the hepatic levels of mRNA for IL-1α and those of IL-1α in serum, with a time profile closely related to that of TNF-α. It is concluded that T3-induced oxidative stress enhances the DNA-binding activity of NF-κB and the NF-κB-dependent expression of TNF-α and IL-10 genes.