IL-33 signalling in liver immune cells enhances drug-induced liver injury and inflammation
Autor: | Brenda Naemi Nakagaki, Valérie F. J. Quesniaux, Débora Moreira Alvarenga, Bruna Araújo David, Bernhard Ryffel, José Carlos Farias Alves Filho, Ariane Barros Diniz, Renata Monti Rocha, Érika de Carvalho, Maria Alice Freitas Lopes, Pedro Marques, Gustavo B. Menezes, Rodrigo Guabiraba Brito, Sarah Cozzer Marchesi, Rafael M. Rezende, Alan Moreira de Araujo, Denise Carmona Cara, Rafaela Vaz Sousa Pereira, Maísa Mota Antunes |
---|---|
Přispěvatelé: | mmunopharmacology, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Laboratório de Imunobiofotônica, Departamento de Morfologia, Universidade Federal de Minas Gerais (UFMG), CNPq, CAPES, FAPEMIG |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Chemokine Neutrophils [SDV]Life Sciences [q-bio] 0302 clinical medicine Medicine Bone Marrow Transplantation Mice Knockout Liver injury Mice Inbred BALB C biology neutrophil Analgesics Non-Narcotic 3. Good health Liver [SDV.IMM]Life Sciences [q-bio]/Immunology Female Chemical and Drug Induced Liver Injury medicine.symptom Intravital microscopy Signal Transduction medicine.drug acetaminophen overdose Immunology Inflammation 03 medical and health sciences Immune system Animals leucocyte Acetaminophen Pharmacology DAMPs business.industry DNA ST2 Interleukin-33 medicine.disease Interleukin-1 Receptor-Like 1 Protein Liver necrosis Interleukin 33 030104 developmental biology IL-33 Hepatocytes Cancer research biology.protein business 030215 immunology |
Zdroj: | Inflammation Research Inflammation Research, Springer Verlag, 2018, 67 (1), pp.77-88. ⟨10.1007/s00011-017-1098-3⟩ |
ISSN: | 1420-908X 1023-3830 |
DOI: | 10.1007/s00011-017-1098-3 |
Popis: | International audience; The aim of this study was to investigate the contribution of IL-33/ST2 axis in the onset and progression of acute liver injury using a mice model of drug-induced liver injury (DILI). DILI was induced by overdose administration of acetaminophen (APAP) by oral gavage in wild-type BALB/c, ST2-deficient mice and in different bone marrow chimeras. Neutrophils were depleted by anti-Ly6G and macrophages with clodronate liposomes (CLL). Blood and liver were collected for biochemical, immunologic and genetic analyses. Mice were imaged by confocal intravital microscopy and liver non-parenchymal cells and hepatocytes were isolated for flow cytometry, genetic and immunofluorescence studies. Acetaminophen overdose caused a massive necrosis and accumulation of immune cells within the liver, concomitantly with IL-33 and chemokine release. Liver non-parenchymal cells were the major sensors for IL-33, and amongst them, neutrophils were the major players in amplification of the inflammatory response triggered by IL-33/ST2 signalling pathway. Blockage of IL-33/ST2 axis reduces APAP-mediated organ injury by dampening liver chemokine release and activation of resident and infiltrating liver non-parenchymal cells. |
Databáze: | OpenAIRE |
Externí odkaz: |