Envolvimento do eixo IL-33 / ST2 no desenvolvimento de lesão hepática aguda

• Ano de defesa: 2017
• Autor(a) principal: Maísa Mota Antunes
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS; Programa de Pós-Graduação em Biologia Celular; UFMG
• Palavras-chave em Português: Leucócitos; Neutrófilos; IL-33; DAMPs; ST2; Necrose hepática; Biologia Celular; Necrose Hepática Massiva; Interleucina-33
• Link de acesso: http://hdl.handle.net/1843/33818

Liver injury is a major health concern and one of the most frequent causes of hepatic failure is the abusive and unsupervised intake of drugs. It is estimated that 50% of the cases of acute liver failure is due to acetaminophen (APAP) abuse. At higher doses, APAP causes hepatocyte necrosis and release of intracellular molecules that – once in the extracellular environment – will trigger a robust inflammatory response. Different cell molecules were already described as damage associated molecular patterns (DAMPs) that are relevant in the context of sterile inflammation, including ATP, high motility group box (HMGB)-1, DNA, histones and also IL-33. IL-33 signals via a single receptor (ST2, or IL1RL1) and the participation of this pathway in liver diseases is still controversial in the literature. Here we demonstrated that IL- 33 signalling via ST2 is central in aggravation of necrosis-triggered liver inflammation. Mice lacking ST2 receptor were resistant to APAP toxic effects, and bone marrow transplantation of ST2-deficent hematopoietic progenitors rescued hepatic failure in wild type mice. Neutrophils are the major sensors for extracellular IL-33, suggesting a rational for future therapeutic approaches designed to dampen IL-33 signalling in immune cells during sterile liver injury.