| Autor: |
Renata Monti-Rocha, Allysson Cramer, Paulo Gaio Leite, Maísa Mota Antunes, Rafaela Vaz Sousa Pereira, Andréia Barroso, Celso M. Queiroz-Junior, Bruna Araújo David, Mauro Martins Teixeira, Gustavo Batista Menezes, Fabiana Simão Machado |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Frontiers in Immunology, Vol 9 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
1664-3224 |
| DOI: |
10.3389/fimmu.2018.03134 |
| Popis: |
Acetaminophen (APAP) is usually safe when administrated in therapeutic doses; however, APAP overdose can lead to severe liver injury. APAP can cause direct hepatocyte damage, and stimulates an inflammatory response leading to oxidative stress. Supressor of Cytokine Signaling (SOCS) 2 modulates cytokine and growth factor signaling, and plays a role in the regulation of hepatic cellular processes. Our study evaluated the role of SOCS2 in APAP liver injury. The administration of a toxic dose (600 mg/kg) of APAP caused significant liver necrosis in WT mice. In SOCS2−/− mice, there was significantly more necrosis, neutrophil recruitment, and expression of the neutrophil-active chemokine CXCL-1. Expression of proinflammatory cytokines, such as TNF-α and IL-6, was elevated, while expression of anti-inflammatory cytokines, IL-10 and TGF-β, was diminished. In vitro, SOCS2−/− hepatocytes expressed more p-NF-kB and produced more ROS than WT hepatocytes when exposed to APAP. SOCS2−/− hepatocytes were more sensitive to cell death in the presence of IL-6 and hydrogen peroxide. The administration of catalase in vitro and in vivo resulted in a pronounced reduction of cells/mice death and necrosis in the SOCS2−/− group. We have demonstrated that SOCS2 has a protective role in the liver by controlling pro-oxidative and inflammatory mechanisms induced by APAP. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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