Thyroid hormone-induced oxidative stress triggers nuclear factor-kappaB activation and cytokine gene expression in rat liver.
Nuclear factor-kappaB (NF-kappaB) is a redox-sensitive factor responsible for the transcriptional activation of cytokine-encoding genes. In this study, we show that 3,3,5-triiodothyronine (T(3)) administration to rats activates hepatic NF-kappaB, 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 alpha-tocopherol and N-acetylcysteine or by the Kupffer cell inactivator gadolinium chloride. Livers from hyperthyroid rats with enhanced NF-kappaB DNA-binding activity show induced mRNA expression of the NF-kappaB-responsive genes for tumor necrosis factor-alpha (TNF-alpha) 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-1alpha and those of IL-1alpha in serum, with a time profile closely related to that of TNF-alpha. It is concluded that T(3)-induced oxidative stress enhances the DNA-binding activity of NF-kappaB and the NF-kappaB-dependent expression of TNF-alpha and IL-10 genes.
Tapia
Gladys
G
Programa de Farmacologíca Molecular y Clínica, Instituto de Ciencias Biomédicas, Universidad de Chile, Santiago, Chile.
Fernández
Virginia
V
Varela
Patricia
P
Cornejo
Pamela
P
Guerrero
Julia
J
Videla
Luis A
LA
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D003720:Densitometry; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D005682:Gadolinium / Q000494:pharmacology; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000378:metabolism*; D013997:Time Factors; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D005609:Free Radicals; D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D013963:Thyroid Hormones; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D012313:RNA; D005682:Gadolinium; C038958:gadolinium chloride; D010100:Oxygen; D000111:Acetylcysteine