Neferine inhibits LPS-ATP-induced endothelial cell pyroptosis via regulation of ROS/NLRP3/Caspase-1 signaling pathway
| Autor: | Yang-Shuo Tang, Qiaoling Zhou, Jiaxi Pu, Yan-Hua Zhao, Yan-Cheng Luo, Yong Zhong, Xiaozhao Li |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Cell Survival Immunology Cell Caspase 1 medicine.disease_cause Benzylisoquinolines Antioxidants 03 medical and health sciences Adenosine Triphosphate 0302 clinical medicine Malondialdehyde NLR Family Pyrin Domain-Containing 3 Protein Human Umbilical Vein Endothelial Cells Pyroptosis medicine Humans RNA Small Interfering Renal Insufficiency Chronic Pharmacology Superoxide Dismutase Cell growth Chemistry Endothelial Cells Inflammasome Cell biology Endothelial stem cell Oxidative Stress 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation 030220 oncology & carcinogenesis Disease Progression Reactive Oxygen Species Intracellular Oxidative stress Signal Transduction medicine.drug |
| Zdroj: | Inflammation Research. 68:727-738 |
| ISSN: | 1420-908X 1023-3830 |
| DOI: | 10.1007/s00011-019-01256-6 |
| Popis: | Oxidative stress-induced endothelial dysfunction and pyroptosis play an important role during chronic kidney disease (CKD) progression. Neferine, which is an alkaloid ingredient from the lotus seed embryo, has many biological actions such as anti-inflammatory, anticancer and antioxidant. However, the role of neferine in endothelial cell pyroptosis and the involved mechanism remain obscure. The aim is to probe the protective effects of neferine on cell pyroptosis and the involved underlying mechanism. After the HUVECs were primed with neferine treatment for 2 h prior to LPS and ATP exposure for 24 h, the cell proliferation was determined by BrdU; the cell LDH release was detected by LDH kits; the levels of intracellular ROS, MDA and SOD were tested by detection kits; Caspase-1 activity kit was used to determine caspase-1 activity; the contents of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD were tested by RT-PCR and western blot. We found that neferine could inhibit LPS-ATP-induced oxidative stress and the activation of NLRP3 inflammasome signaling, and increased the endothelial cell viability and SOD production. siRNA which mediated the knockdown of NLRP3 promoted the neferine-induced inhibition effects of cell pyroptosis. Furthermore, these neferine-induced effects were reversed by the over-expression of NLRP3. Our findings indicated neferine may reduce ROS by anti-oxidation and inhibit LPS-ATP-induced endothelial cell pyroptosis via blocking ROS/NLRP3/Caspase-1 signaling pathway, which provides the evidence for therapeutic effect in CKD. |
| Databáze: | OpenAIRE |
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