title: Thyroid hormone suppresses ischemia-reperfusion-induced liver NLRP3 inflammasome activation: Role of AMP-activated protein kinase.
abstract: Thyroid hormone (T3) induces liver preconditioning (PC) against ischemia-reperfusion (IR), a response energetically supported by AMP-activated protein kinase (AMPK) upregulation. The aim of this work is to evaluate the influence of T3on IR-induced liver NLRP3 inflammasome activation and the relevance of AMPK activity on liver injury by the use of the AMPK inhibitor compound C (CC). Male Sprague-Dawley rats were given 0.1mgT3/kg (time zero) and 10mg CC/kg (time zero and 24h) or the respective vehicles, and subjected to 1h ischemia-20h reperfusion 48h after hormone treatment. Measurements included parameters of liver injury, hepatic levels of mRNAs (qPCR) and proteins (Western Blot or ELISA). IR induced substantial distortion of liver architecture, hepatocyte necrosis, and neutrophil infiltration with increased serum aspartate aminotransferase (AST) levels. T3suppressed IR liver injury and AST enhancement, effects that were reverted by CC. Concomitantly, IR-induced liver mRNA and protein expression of NLRP3 and interleukin-1β (IL-1β) were restrained by T3, whereas CC eliminated T3-dependent PC. In conclusion, in vivo T3administration triggers liver PC against IR injury by suppressing the inflammatory response associated with hepatic NLRP3 and IL-1β upregulation, with AMPK playing a causal role regulating energy dynamics to upkeep PC.
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Romina
authors.initials: R
authors.lastname: Vargas
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile. Electronic address: lvidela@med.uchile.cl.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Videla
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D051381:Rats; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013963:Thyroid Hormones / Q000378:metabolism* / Q000494:pharmacology; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology
chemical_list: D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D013963:Thyroid Hormones; D014284:Triiodothyronine; D055372:AMP-Activated Protein Kinases
keywords: 3,3′,5-triiodothyronine; AMP-activated protein kinase; Compound C; Ischemia-reperfusion liver injury; NLRP3 inflammasome