The acute-phase response of the liver in relation to thyroid hormone-induced redox signaling.
Recently, we reported that 3,3',5-triiodothyronine (T3) induces the expression of redox-sensitive genes as a nongenomic mechanism of T3 action. In this study, we show that T3 administration to rats (daily doses of 0.1 mg/kg ip for 3 consecutive days) induced a calorigenic response and liver glutathione depletion as an indication of oxidative stress, with higher levels of interleukin (IL)-6 in serum (ELISA) and hepatic STAT3 DNA binding (EMSA), which were maximal at 48-72 h after treatment. Under these conditions, the protein expression of the acute-phase proteins haptoglobin and beta-fibrinogen is significantly augmented, a change that is suppressed by pretreatment with alpha-tocopherol (100 mg/kg ip) or gadolinium chloride (10 mg/kg iv) before T3. It is concluded that T3 administration induces the acute-phase response in rat liver by a redox mechanism triggered at the Kupffer cell level, in association with IL-6 release and activation of the STAT3 cascade, a response that may contribute to reestablishing homeostasis in the liver and extrahepatic tissues exhibiting oxidative stress.
Tapia
Gladys
G
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 7, Chile.
Fernández
Virginia
V
Pino
Cesar
C
Ardiles
Rodrigo
R
Videla
Luis A
LA
D000210:Acute-Phase Reaction / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006242:Haptoglobins / Q000187:drug effects / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014284:Triiodothyronine / Q000494:pharmacology*
C115499:BBeta fibrinogen; D006242:Haptoglobins; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D014284:Triiodothyronine; D005340:Fibrinogen; D005978:Glutathione