A new form of amphotericin B - the complex with copper (II) ions - downregulates sTNFR1 shedding and changes the activity of genes involved in TNF-induced pathways AmB-Cu2+ downregulates sTNFR1 shedding and changes the activity of genes involved in TNF-induced pathways

被引：6

作者：

Gola, Joanna ^{[1
]}

Strzalka-Mrozik, Barbara ^{[1
]}

Kruszniewska-Rajs, Celina ^{[1
]}

Janiszewski, Adrian ^{[1
]}

Skowronek, Bartlomiej ^{[1
]}

Gagos, Mariusz ^{[2
]}

Czernel, Grzegorz ^{[3
]}

Mazurek, Urszula ^{[1
]}

机构：

[1] Med Univ Silesia, Dept Mol Biol, Sch Pharm, Div Lab Med Sosnowiec, Katowice, Poland

[2] Marie Curie Sklodowska Univ, Inst Biol & Biotechnol, Dept Cell Biol, Lublin, Poland

[3] Univ Life Sci Lublin, Dept Biophys, Lublin, Poland

来源：

PHARMACOLOGICAL REPORTS | 2017年 / 69卷 / 01期

关键词：

Amphotericin B; Copper complexes; Oligonucleotide microarrays; Real-time RT-qPCR; TNF; INFLAMMATORY RESPONSE; CANDIDA-ALBICANS; HUMAN MONOCYTES; EXPRESSION; RECEPTORS; ALPHA; CELLS; NEPHROTOXICITY; INHIBITOR; CYTOKINES;

D O I：

10.1016/j.pharep.2016.09.008

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Background: A new form of amphotericin B (AmB)-complex with copper (II) ions (AmB-Cu2+) - 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-Cu2+, 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-Cu2+ 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-Cu2+- and AmB-ox-treated cells. TNFR1 mRNA was downregulated in AmB-ox, while TNFR2 mRNAwas up regulated in AmB and AmB-Cu2(2+). Several changes in the expression of TNF-related genes coincided with changes in the expression of TNF receptors. Conclusions: The lower toxicity of AmB-Cu2+ 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. (C) 2016 Published by Elsevier Sp. z o.o. on behalf of Institute of Pharmacology, Polish Academy of Sciences.

引用

页码：22 / 28

页数：7

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