ArticleClinical and experimental immunology2018
Synergistic effect of interleukin-17 and tumour necrosis factor-α on inflammatory response in hepatocytes through interleukin-6-dependent and independent pathways.
Article in Clinical and experimental immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 57 citations in OpenAlex.
- Calcipotriol-betamethasone foam modulates serum and tissue IL-17A, IL-31, IL-31RA, and substance P in mild-to-moderate psoriatic itch: A clinical and immunopathological study.JID innovations : skin science from molecules to population health · 2026Article
- Development and validation of a clinically applicable biomarker panel for identifying autoimmune type IIb chronic spontaneous urticaria.The World Allergy Organization journal · 2026Article
- Mume Flos ameliorates MASLD-associated cognitive impairment by attenuating IL-17/NF-κB-mediated metabolic neuroinflammation.Metabolic brain disease · 2026Article
- Positive and Negative Cardiovascular Effects of JAK Inhibitors in Inflammation.ACR open rheumatology · 2026Review
- IL17FMolecular medicine (Cambridge, Mass.) · 2026Article
- Analysis of C-Reactive Protein and Nitric Oxide Serum Levels in Hypertensive Incidence of Aceh Population, Indonesia.International journal of preventive medicine · 2026Article
- Advances in the Molecular Mechanisms of Pulmonary Fibrosis in Systemic Sclerosis: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Effects of transcatheter tricuspid valve replacement on hepatic and renal function in severe TR.International journal of cardiology. Heart & vasculature · 2025Article
- Oral probiotic extracellular vesicle therapy mitigates Influenza A Virus infection via blunting IL-17 signaling.Bioactive materials · 2025Article
- The Microbiome Modifies Manifestations of Hemophagocytic Lymphohistiocytosis in Perforin-Deficient Mice.European journal of immunology · 2025Article
- Article
- Association between C-reactive protein to albumin ratio and subclinical myocardial injury in the general population free from cardiovascular disease.Journal of cardiothoracic surgery · 2024Article
- Transcriptome analysis revealed that ischemic post-conditioning suppressed the expression of inflammatory genes in lung ischemia-reperfusion injury.Frontiers in genetics · 2024Article
- Role of the type 3 cytokines IL-17 and IL-22 in modulating metabolic dysfunction-associated steatotic liver disease.Frontiers in immunology · 2024Review
- Inflammation, mitochondrial dysfunction and physical performance: a possible association in older patients with persistent atrial fibrillation-the results of a preliminary study.Aging clinical and experimental research · 2023Article
- Inflammatory Cytokines Associated with Multiple Sclerosis Directly Induce Alterations of Neuronal Cytoarchitecture in Human Neurons.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- IL-6 at the center of cytokine storm: Circulating inflammation mediators as biomarkers in hospitalized COVID-19 patients.Journal of clinical laboratory analysis · 2023Article
- Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease.Cell host & microbe · 2023Article
- Liver Regeneration and Immunity: A Tale to Tell.International journal of molecular sciences · 2023Review
- A single targeted gamma-ray irradiation induced an acute modulation of immune cells and related cytokines in EMT6 mouse-bearing tumour model.Cancer biomarkers : section A of Disease markers · 2023Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proinflammatory cytokines interleukin (IL)-17 and tumour necrosis factor (TNF)-α are targets for treatment in many chronic inflammatory diseases. Here, we examined their role in liver inflammatory response compared to that of IL-6. Human hepatoma cells (HepaRG, Huh7.5 and HepG2 cells) and primary human hepatocytes (PHH) were cultured with IL-6, IL-17 and/or TNF-α. To determine the contribution of the IL-6 pathway in the IL-17/TNF-α-mediated effect, an anti-IL-6 receptor antibody was used. IL-17 and TNF-α increased in synergy IL-6 secretion by HepaRG cells and PHH but not by Huh7.5 and HepG2 cells. This IL-17/TNF-α synergistic cooperation enhanced the levels of C-reactive protein (CRP) and aspartate aminotransferase (ASAT) in HepaRG cell and PHH cultures through the induction of IL-6. IL-17/TNF-α also up-regulated IL-8, monocyte chemoattractant protein (MCP)-1 and chemokine (C-C motif) ligand 20 (CCL20) chemokines in synergy through an IL-6-independent pathway. Interestingly, first exposure to IL-17, but not to TNF-α, was crucial for the initiation of the IL-17/TNF-α synergistic effect on IL-6 and IL-8 production. In HepaRG cells, IL-17 enhanced IL-6 mRNA stability resulting in increased IL-6 protein levels. The IL-17A/TNF-α synergistic effect on IL-6 and IL-8 induction was mediated through the activation of extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase, nuclear factor-κB and/or protein kinase B (Akt)-phosphatidylinositol 3-kinase signalling pathways. Therefore, the IL-17/TNF-α synergistic interaction mediates systemic inflammation and cell damage in hepatocytes mainly through IL-6 for CRP and ASAT induction. Independently of IL-6, the IL-17A/TNF-α combination may also induce immune cell recruitment by chemokine up-regulation. IL-17 and/or TNF-α neutralization can be a promising therapeutic strategy to control both systemic inflammation and liver cell attraction.
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