Etanercept attenuates immune-mediated hepatitis induced by concanavalin A via differential regulation of the key effector cytokines of CD4+ T cells
| Autor: | Nashwa M Abu-Elsaad, Tarek Ibrahim, Mahmoud Elshal, Amr El-Karef |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Male Anti-Inflammatory Agents Pharmacology 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology Etanercept Hepatitis Pathogenesis 03 medical and health sciences Mice 0302 clinical medicine Immune system medicine Concanavalin A Animals General Pharmacology Toxicology and Pharmaceutics Interleukin 4 Liver injury Mice Inbred BALB C biology Effector business.industry General Medicine medicine.disease 030104 developmental biology biology.protein Cytokines Signal transduction Chemical and Drug Induced Liver Injury Mitogens business Immunosuppressive Agents medicine.drug Signal Transduction |
| Zdroj: | Life sciences. 277 |
| ISSN: | 1879-0631 |
| Popis: | Aims The current study aims to investigate the role of the key effector cytokines produced by CD4+T cells in the pathogenesis of Con A-induced liver injury in mice and testing whether etanercept can be repurposed to differentially regulate these cytokines. Main methods Four groups of mice were used: group I: control group, group II: mice received 15 mg/kg Con A i.v, group III: mice received 15 mg/kg etanercept i.p, group IV: mice received both Con A and etanercept as described. Hepatic injury and necroinflammation were assessed. Infiltration of CD4+ T cells and neutrophils were evaluated. Hepatic levels of TNF-α, IL-4, IL-10, and MDA were assigned and expression of NF-κB as well. Key findings A significant decrease in ALT, AST, and LDH levels occurred when etanercept was injected before Con A. Hepatic necrosis and infiltration of CD4+ T cells and neutrophils were reduced by etanercept. Levels of TNF-α, IL-4, and MDA were significantly decreased in group IV compared to group II while that of IL-10 was increased. Also, number of NF-κB positive cells was significantly low in group IV. Significance The study elucidates an interplay between the two effector cytokines of CD4+ T cells, TNF-α and IL-4, and their key role in Con A-induced liver injury. Additionally, our results showed that etanercept could be repurposed to differentially regulate effector cytokines produced by CD4+ T cells. Not only TNF-α, but also IL-4 signaling pathways, through which it exerts immunomodulatory, anti-inflammatory, and anti-oxidant effects leading to attenuation of Con A-induced liver injury. |
| Databáze: | OpenAIRE |
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