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IL-33 signalling in liver immune cells enhances drug-induced liver injury and inflammation
- Source :
- Inflammation Research, Inflammation Research, Springer Verlag, 2018, 67 (1), pp.77-88. ⟨10.1007/s00011-017-1098-3⟩
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 1420908X and 10233830
- Volume :
- 67
- Database :
- OpenAIRE
- Journal :
- Inflammation Research
- Accession number :
- edsair.doi.dedup.....df7014ce2f12b9f63bcb4536b1b7214b