PMID- 34688696 OWN - NLM STAT- MEDLINE DCOM- 20220217 LR - 20220217 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 291 DP - 2022 Feb 15 TI - The protective effect of quercetin on macrophage pyroptosis via TLR2/Myd88/NF-kappaB and ROS/AMPK pathway. PG - 120064 LID - S0024-3205(21)01051-1 [pii] LID - 10.1016/j.lfs.2021.120064 [doi] AB - AIMS: Pyroptosis is a pro-inflammatory form of programmed cell death, which plays a vital role in the development of inflammatory diseases. As a natural flavonoid, quercetin has been shown to possess anti-inflammatory activity, but its effects on macrophage pyroptosis is still unclear. Therefore, this study aims to investigate the effects of quercetin on macrophage pyroptosis and the underlying mechanism. MATERIAL AND METHODS: LPS/ATP treatment was used to induce THP-1 macrophage pyroptosis. Cell counting kit-8 (CCK-8) assay was used to evaluate cell viability. Scanning electron microscope (SEM) was used to detect cell morphology. Hoechst/propidium iodide (PI) staining and lactate dehydrogenase (LDH) assay were performed to evaluate the cell membrane integrity. The expression of key components and effectors of nod-like receptors3 (NLRP3) inflammasome were examined by real-time PCR and western blot. Immunofluorescence staining was used to detect reactive oxygen species (ROS) level and P65 nuclear translocation. KEY FINDINGS: Our results showed that quercetin prevented THP-1 macrophage pyroptosis by reducing the expression of NLRP3 and cleaved-caspase1, as well as IL-1beta and N-GSDMD in a concentration dependent manner. Quercetin suppressed NLRP3 inflammasome activation by inhibiting ROS overproduction. Moreover, quercetin inhibited the phosphorylation of P65 and its translocation from cytoplasm into nuclear. In addition, we found that quercetin suppressed the increase of TLR2/Myd88 and p-AMPK induced by LPS/ATP, while both TLR2 and AMPK agonist weakened the inhibitory effect of quercetin on the activity of NLRP3 inflammasome and alleviated the protective effect on macrophages pyroptosis. SIGNIFICANCE: Quercetin possesses a protective effect on macrophages pyroptosis via TLR2/Myd88/NF-kappaB and ROS/AMPK pathway. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Luo, Xing AU - Luo X AD - Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China; Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin 150001, PR China. FAU - Bao, Xiaoyi AU - Bao X AD - Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China; Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin 150001, PR China. FAU - Weng, Xiuzhu AU - Weng X AD - Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China. FAU - Bai, Xiaoxuan AU - Bai X AD - Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China. FAU - Feng, Yi AU - Feng Y AD - Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin 150001, PR China. FAU - Huang, Jianxin AU - Huang J AD - Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin 150001, PR China. FAU - Liu, Shaoyu AU - Liu S AD - Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin 150001, PR China; Bin xian People's Hospital, Harbin 150400, PR China. FAU - Jia, Haibo AU - Jia H AD - Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China; Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin 150001, PR China. Electronic address: jhb101180@163.com. FAU - Yu, Bo AU - Yu B AD - Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China; Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin 150001, PR China. LA - eng PT - Journal Article DEP - 20211021 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Inflammasomes) RN - 0 (MYD88 protein, human) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NF-kappa B) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (NLRP3 protein, human) RN - 0 (Reactive Oxygen Species) RN - 0 (TLR2 protein, human) RN - 0 (Toll-Like Receptor 2) RN - 9IKM0I5T1E (Quercetin) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - EC 2.7.4.3 (Adenylate Kinase) RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Adenylate Kinase/metabolism MH - Anti-Inflammatory Agents/pharmacology MH - Caspase 1/metabolism MH - Cell Survival/drug effects MH - Humans MH - Inflammasomes/metabolism MH - Macrophages/drug effects/*metabolism MH - Myeloid Differentiation Factor 88/metabolism MH - NF-kappa B/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Pyroptosis/drug effects/*physiology MH - Quercetin/metabolism/*pharmacology MH - Reactive Oxygen Species/metabolism MH - THP-1 Cells MH - Toll-Like Receptor 2/metabolism OTO - NOTNLM OT - Macrophage OT - NF-kappaB pathway OT - NLRP3 inflammasome OT - Pyroptosis OT - Quercetin OT - ROS EDAT- 2021/10/25 06:00 MHDA- 2022/02/19 06:00 CRDT- 2021/10/24 20:33 PHST- 2021/07/12 00:00 [received] PHST- 2021/10/05 00:00 [revised] PHST- 2021/10/14 00:00 [accepted] PHST- 2021/10/25 06:00 [pubmed] PHST- 2022/02/19 06:00 [medline] PHST- 2021/10/24 20:33 [entrez] AID - S0024-3205(21)01051-1 [pii] AID - 10.1016/j.lfs.2021.120064 [doi] PST - ppublish SO - Life Sci. 2022 Feb 15;291:120064. doi: 10.1016/j.lfs.2021.120064. Epub 2021 Oct 21.