Background: A new form of amphotericin B (AmB)- complex with copper (II) ions (AmB-Cu) - is less toxic to human renal cells. Cytokines, including Tumor Necrosis Factor (TNF), are responsible for nephrotoxicity observed in patients treated with AmB. Another problem during therapy is the occurrence of oxidized forms of AmB (AmB-ox) in patients' circulation. To elucidate the molecular mechanism responsible for the reduction of the toxicity of AmB-Cu, we evaluated the expression of genes encoding TNF and its receptors alongside encoding proteins involved in TNF-induced signalization.
Methods: Renal cells (RPTECs) were treated with AmB, AmB-Cu or AmB-ox. The expression of TNF and its receptors was evaluated by ELISA tests and real-time RT-qPCR. The expression of TNF-related genes was appointed using oligonucleotide microarrays.
Results: Only sTNFR1 was detected, and its level was lower in AmB-Cu- and AmB-ox-treated cells. TNFR1 mRNA was downregulated in AmB-ox, while TNFR2 mRNA was upregulated in AmB and AmB-Cu. Several changes in the expression of TNF-related genes coincided with changes in the expression of TNF receptors.
Conclusions: The lower toxicity of AmB-Cu could result from the changes in the expression of TNF receptors, which coincided with the changes in the expression of genes encoding proteins involved in TNF-induced pathways. This situation might subsequently result in a changes in intracellular signalization and influence the toxicity of tested forms of AmB on renal cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.pharep.2016.09.008 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
TNF-ɑ induces mitochondrial dysfunction to drive NLRP3/Caspase-1/GSDMD-mediated pyroptosis in MCF-7 cells.
Sci Rep
October 2024
Department of Anatomy, Mudanjiang Medical University, Mudanjiang City, 157000, Heilongjiang, China.
Pyroptosis is a gasdermin-mediated pro-inflammatory form of programmed cell death (PCD). Tumor necrosis factor-ɑ (TNF-ɑ) is an inflammatory cytokine, and some studies have shown that TNF-ɑ can cause pyroptosis of cells and exert anti-tumor effects. However, whether TNF-ɑ exerts anti-tumor effects on breast cancer cells by inducing pyroptosis has not been reported.
View Article and Find Full Text PDFAnalgesic and Anti-Arthritic Potential of Methanolic Extract and Palmatine Obtained from Leaves.
Pharmaceuticals (Basel)
October 2024
Health Sciences College, Federal University of Grande Dourados (UFGD), Dourados 79804-970, MS, Brazil.
: is used in folk medicine to treat pain and arthritis. Palmatine is an alkaloid isolated from several plants, including leaves. The aim of the present study was to investigate the analgesic, anti-arthritic, and anti-inflammatory potential of the methanolic extract of (EMAS) and palmatine.
View Article and Find Full Text PDFCeramide metabolism alterations contribute to Tumor Necrosis Factor-induced melanoma dedifferentiation and predict resistance to immune checkpoint inhibitors in advanced melanoma patients.
Front Immunol
August 2024
Unité Mixte de Recherche Intitut National de la Santé et de la Recherche Médicale (INSERM) 1037, Centre National de la Recherche Scientifique (CNRS) 5071, Université Toulouse III - Paul Sabatier, Centre de Recherches en Cancérologie de Toulouse (CRCT), Toulouse, France.
Introduction: Advanced cutaneous melanoma is a skin cancer characterized by a poor prognosis and high metastatic potential. During metastatic spread, melanoma cells often undergo dedifferentiation toward an invasive phenotype, resulting in reduced expression of microphthalmia-associated transcription factor (MITF)-dependent melanoma antigens and facilitating immune escape. Tumor Necrosis Factor (TNF) is known to be a key factor in melanoma dedifferentiation.
View Article and Find Full Text PDFCyld restrains the hyperactivation of synovial fibroblasts in inflammatory arthritis by regulating the TAK1/IKK2 signaling axis.
Cell Death Dis
August 2024
Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center (BSRC) "Alexander Fleming", Vari, Greece.
TNF is a potent cytokine known for its involvement in physiology and pathology. In Rheumatoid Arthritis (RA), persistent TNF signals cause aberrant activation of synovial fibroblasts (SFs), the resident cells crucially involved in the inflammatory and destructive responses of the affected synovial membrane. However, the molecular switches that control the pathogenic activation of SFs remain poorly defined.
View Article and Find Full Text PDFSystematic review: Methotrexate-A poorly understood and underused medication in inflammatory bowel disease.
Aliment Pharmacol Ther
September 2024
Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy, France.
Background: Methotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared to thiopurines.
Aims: To review the efficacy, safety, optimal dosing and delivery regimens of methotrexate in adults with IBD.
Methods: We conducted a systematic review of studies involving patients with IBD treated with methotrexate from inception to August 2023.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!