Review
Cell Biology
Jie Gao, Hongliang Zhang, Yanyan Yang, Jinhui Tao
Summary: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a cytoplasmic multiprotein complex involved in innate immune response. Its aberrant activation is associated with various inflammatory diseases including rheumatoid arthritis (RA). This review discusses the current understanding of NLRP3 activation in RA pathogenesis and its impact on innate and adaptive immunity, as well as the potential application of specific NLRP3 inhibitors as therapeutic strategies for RA.
Article
Medicine, Research & Experimental
Xinyu Yang, Ning Zhan, Yang Jin, Hanzhi Ling, Chipeng Xiao, Zhen Xie, Hao Zhong, Xinxin Yu, Runhua Tang, Jinglan Ma, Jubo Guan, Guoyu Yin, Gan Wu, Liangjing Lu, Jianguang Wang
Summary: Tofacitinib (TOF) restores the balance of gamma delta regulatory T-cells/gamma delta T17 cells in rheumatoid arthritis (RA) patients by reducing levels of gamma delta T17 cell-related cytokine and inhibiting excessive NLRP3 inflammasome activation.
Article
Multidisciplinary Sciences
Umeharu Ohto, Yukie Kamitsukasa, Hanako Ishida, Zhikuan Zhang, Karin Murakami, Chie Hirama, Sakiko Maekawa, Toshiyuki Shimizu
Summary: This study reveals the cryo-electron microscopy structure of the dodecameric form of NLRP3 and its binding site with the inhibitor MCC950. It provides insights into the role of NLRP3 in membrane association and activation, offering potential targets for drug development.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Yuhua Shi, Qian Lv, Mengjie Zheng, Hongxiang Sun, Fushan Shi
Summary: INF39 is a specific inhibitor for NLRP3 inflammasome activation, without affecting other inflammasomes. It exerts its anti-inflammatory effect by inhibiting the interaction of NEK7-NLRP3 and other downstream events.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Review
Physiology
Lina Emilia Werner, Ulf Wagner
Summary: This review summarizes the important role of the calcium-sensing receptor (CaSR) in inflammatory processes, with a focus on its significance for monocytes in rheumatoid arthritis. Stimulation of the receptor by increased extracellular Ca2+ can trigger a pro-inflammatory response and IL-1 beta release. Increased uptake of Ca2+ and IL-1 beta release is associated with more active disease in rheumatoid arthritis, while CaSR overexpression is linked to cardiovascular complications.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Weijie Li, Xia Mao, Xiaoyue Wang, Yudong Liu, Kexin Wang, Congchong Li, Taixian Li, Yanqiong Zhang, Na Lin
Summary: Baihu-Guizhi decoction (BHGZD), a traditional Chinese medicine-originated prescription, has shown promising therapeutic effects in the treatment of rheumatoid arthritis (RA) by modulating the TLR4-mediated inflammasome activation. BHGZD not only alleviated RA symptoms in animal models but also inhibited pyroptosis and inflammatory signaling pathways in vitro, suggesting its potential as an immunomodulatory and anti-inflammatory agent in RA treatment.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Immunology
Ming Jing, Junjie Yang, Lirong Zhang, Jing Liu, Sen Xu, Meiling Wang, Leiming Zhang, Yue Sun, Weibin Yan, Guige Hou, Chunhua Wang, Wenyu Xin
Summary: The study demonstrates that Celastrol effectively alleviates rheumatoid arthritis (RA) symptoms by inhibiting the activation of the NF-κB signaling pathway and NLRP3 inflammasome, ultimately suppressing inflammation. Celastrol also inhibits ROS production induced by LPS and ATP, suggesting a potential therapeutic mechanism for treating RA.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Hao-yu Wang, Xi Lin, Guan-gen Huang, Rong Zhou, Shu-yue Lei, Jing Ren, Kai-rong Zhang, Chun-lan Feng, Yan-wei Wu, Wei Tang
Summary: This study shows that Atranorin, a secondary metabolite of lichen family, effectively inhibits NLRP3 inflammasome activation in macrophages and dendritic cells. It binds to ASC protein directly and restricts ASC oligomerization, leading to the suppression of cytokine secretion and cell pyroptosis. Atranorin exhibits therapeutic effects in various NLRP3 inflammasome-driven diseases.
ACTA PHARMACOLOGICA SINICA
(2023)
Review
Immunology
Yi Xiao, Li Zhang
Summary: The NLRP3 inflammasome plays a crucial role in regulating host immune function and its activation leads to cell pyroptosis and inflammatory cytokine production, affecting the development of arthritis. Recent studies have investigated the impact of NLRP3 inflammasome-mediated pyroptosis on various forms of arthritis and explored intervention approaches targeting this process. These findings offer new insights for the clinical identification and treatment of arthritis.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Qi Jiang, Xin Wang, Enyu Huang, Qiao Wang, Chengping Wen, Guocan Yang, Liwei Lu, Dawei Cui
Summary: Inflammasome is a cellular complex involved in the innate inflammatory response, and its excessive or abnormal activation has been implicated in various diseases. In rheumatoid arthritis, inflammasome activation plays a key role in immune dysregulation and joint inflammation. This review summarizes recent research on inflammasome activation and its effector mechanisms in the pathogenesis of rheumatoid arthritis, as well as potential therapeutic strategies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
David M. Calcagno, Angela Chu, Susanne Gaul, Nika Taghdiri, Avinash Toomu, Aleksandra Leszczynska, Benedikt Kaufmann, Bettina Papouchado, Alexander Wree, Lukas Geisler, Hal M. Hoffman, Ariel E. Feldstein, Kevin R. King
Summary: Activation of NLRP3 causes chronic extramedullary myelopoiesis in the liver, leading to inflammation and fibrosis. This activation also down-regulates metabolic pathways in hepatocytes and shifts hepatic stellate cells towards an activated profibrotic state.
Article
Plant Sciences
Xiaoli Jiang, Zhuojian Lu, Qian Zhang, Jialin Yu, Dong Han, Jinhong Liu, Ping Li, Fei Li
Summary: This study aimed to explore the potential targets and molecular mechanisms of Osthole (OST) against rheumatoid arthritis (RA). The results showed that OST's anti-RA effect was mainly related to its anti-inflammatory effect, and AMPK was identified as a potential target. By regulating mitochondrial homeostasis and function, OST effectively inhibited the secretion of inflammatory factors and achieved beneficial effects in the treatment of RA.
Article
Immunology
Asta Luciunaite, Indre Dalgediene, Rapolas Zilionis, Kristina Masalaite, Milda Norkiene, Andrius Sinkunas, Alma Gedvilaite, Indre Kucinskaite-Kodze, Aurelija Zvirbliene
Summary: This study investigates the effect of viral oligomeric proteins on the inflammatory response in macrophages. It finds that filamentous proteins do not induce inflammation, while spherical proteins mediate an inflammatory response and activate the NLRP3 inflammasome.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Allergy
Arinna Bertoni, Federica Penco, Hilaria Mollica, Paola Bocca, Ignazia Prigione, Anna Corcione, Davide Cangelosi, Francesca Schena, Genny Del Zotto, Adriana Amaro, Noemi Paladino, Emanuele Pontali, Marcello Feasi, Sara Signa, Marta Bustaffa, Roberta Caorsi, Serena Palmeri, Paola Contini, Raffaele De Palma, Ulrich Pfeffer, Paolo Uva, Anna Rubartelli, Marco Gattorno, Stefano Volpi
Summary: This study reveals the crucial role of IL-1 beta in driving inflammatory phenotypes in severe COVID-19 patients, whose maturation and secretion are regulated by inflammasomes. The findings suggest that targeting IL-1 beta could be an effective strategy for treating COVID-19 and provide a mechanistic explanation for the strong inflammatory manifestations associated with the disease.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Environmental Sciences
Li Jing, Dan Zheng, Xuejing Sun, Zhixiong Shi
Summary: In this study, it was found that DBDPE could cause aortic endothelial injury and cell pyroptosis. Specifically, DBDPE activated the NOD-like receptor signaling pathway, involving NLRP3 and IL-18. RIPK2 knockdown was shown to inhibit the activation of this pathway and decrease cell death. It was also demonstrated that DBDPE could induce ROS generation and activate NLRP3 inflammasome through upregulation of the NOD-like receptor signaling pathway.
ENVIRONMENTAL POLLUTION
(2023)
