Article
Cell Biology
Hwansu Kang, Eunhui Seo, Yoon Sin Oh, Hee-Sook Jun
Summary: Inflammation contributes to liver disease, and inflammasome activation plays a major role in amplifying liver inflammation. This study investigated the involvement of transforming growth factor-beta (TGF-beta) in inflammasome-mediated fibrosis in hepatic stellate cells. The results showed that TGF-beta increased the activation of NLRP3 inflammasome signaling and the expression of p-Smad2/3-NOX4, leading to increased ROS content and NLRP3 inflammasome activation. NEK7 and active caspase-1 expression were also elevated in TGF-beta-induced cells. Furthermore, TGF-beta secretion levels were significantly increased, and IL-1 beta receptor antagonist treatment inhibited its production. These findings suggest that TGF-beta may act as a danger signal to activate the NLRP3 inflammasome in an autocrine manner, and targeting the NLRP3 inflammasome could be a promising approach for treating TGF-beta-induced liver fibrosis.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Wen-Jing Zhong, Tian Liu, Hui-Hui Yang, Jia-Xi Duan, Jin-Tong Yang, Xin-Xin Guan, Jian-Bing Xiong, Yan-Feng Zhang, Chen-Yu Zhang, Yong Zhou, Cha-Xiang Guan
Summary: The activation of the triggering receptor expressed on myeloid cells-1 (TREM-1) can potentiate acute lung injury (ALI) and induce inflammation, but the underlying mechanism is unclear. This study found that blocking TREM-1 can attenuate the activation of NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome and glycolysis in LPS-induced ALI mice. Furthermore, TREM-1 activation enhances glycolysis and inhibits oxidative phosphorylation in macrophages, and this effect is dependent on the hypoxia-inducible factor-1a (HIF-1 alpha)/mTOR/glycolysis pathway. Inhibiting mTOR or HIF-1 alpha can suppress TREM-1-induced metabolic reprogramming and NLRP3/caspase-1 activation. These findings reveal a novel mechanism of TREM-1-mediated NLRP3 inflammasome activation through the mTOR/HIF-1 alpha/glycolysis pathway.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Qingqing Ke, Caifeng Shi, Yunhui Lv, Lulu Wang, Jing Luo, Lei Jiang, Junwei Yang, Yang Zhou
Summary: This study analyzed the anti-fibrotic and anti-inflammatory effects of the SGLT2 inhibitor dapagliflozin on renal alternations. It was found that dapagliflozin mitigated inflammation and accumulation of metabolites in fibrosis renal tissue through the modulation of metabolism and immune-responsive genes. The study also demonstrated that dapagliflozin blocked the activation of the NLRP3 inflammasome, protecting the kidney from fibrosis development. This research identifies a novel mechanism coupling metabolism and inflammation for the kidney benefits of SGLT2 inhibition.
Article
Medicine, General & Internal
Qimei Luo, Qinghua Hu, Qingkun Zheng, Lewei Gong, Lijuan Su, Baojun Ren, Yongle Ju, Zhanjun Jia, Xianrui Dou
Summary: The study showed that in PD patients, mPGES-1-derived PGE2 plays a critical role in peritoneal fibrosis through activation of the NLRP3 inflammasome, suggesting that targeting mPGES-1 may offer a novel strategy to treat peritoneal fibrosis during PD.
FRONTIERS IN MEDICINE
(2021)
Article
Immunology
Benedikt Jaeger, Benjamin Seeliger, Oliver Terwolbeck, Gregor Warnecke, Tobias Welte, Meike Mueller, Christian Bode, Antje Prasse
Summary: The NLRP3 inflammasome was found to be hyper-inducible in IPF and potentially plays a significant role in the pathogenesis of IPF and IPF-AE, with its activation potentially mediated by reactive oxygen species and cathepsin-B.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Maggie Lam, Ashley Mansell, Michelle D. Tate
Summary: This review discusses the beneficial effects of targeting the NLRP3 inflammasome in silicosis, where inhibition of this inflammasome can eliminate inflammation and fibrosis. However, clinical studies are needed to explore the role of NLRP3 inflammasomes in the clinical setting and to identify biomarkers for early detection of silicosis.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Immunology
Zhe Song, Li Wang, Yongxia Cao, Zihan Liu, Mingliang Zhang, Zhizi Zhang, Shan Jiang, Ruifeng Fan, Ting Hao, Ruyue Yang, Bingshun Wang, Zhenzhen Guan, Lina Zhu, Zhentao Liu, Shuya Zhang, Liang Zhao, Zhihao Xu, Haiwei Xu, Guifu Dai
Summary: This study firstly reported that (8R-12S)-isoandrographolide (ISA) from Andrographis paniculata can reduce pulmonary inflammation and fibrosis by inhibiting NLRP3, improving silicosis. ISA administration alleviated lung injury, attenuated inflammatory response, EMT, and collagen deposition in silica-induced mice. Further studies confirmed that ISA inhibited the expressions of NLRP3 inflammasome-related proteins, leading to the reduction of inflammation and EMT.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xun Guo, Yang Zhang, Chang Liu, Lili Ren, Shuang Gao, Jing Bi, Jia Liang, Peng Wang
Summary: This study found that B3galt2 has neuroprotective effects in ischemic stroke by regulating oxidative stress and NLRP3 inflammasome, mainly through enhancing the TGF-beta 1 pathway.
Article
Cell Biology
Tejal Gandhi, Anjali Patel, Dayashankar Gupta, Harsh Pandya, Atulsingh Chandel
Summary: The objective of this study is to attenuate cardiac fibrosis by inhibiting NLRP3 inflammasome and related genes in a rat model. The results show that the anti-diabetic drug Glibenclamide treats cardiac fibrosis by inhibiting the TGF-beta 1-pSmad2/3-NLRP3 cascade.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Hung-Jen Shih, Chao-Yuan Chang, Chung-Howe Lai, Chun-Jen Huang
Summary: The NLRP3 inflammasome-related TGF-β/Smad signaling pathway plays a crucial role in IC/BPS, and modulation of this pathway, such as using curcumin, can effectively mitigate the sequelae of chronic inflammation-induced bladder injury.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Tuling Li, Xiaomeng Li, Yixian Hao, Jinpeng Liu, Bo Bao, Zhaohui Yang, Mengxian Zhou, Huixia Wei, Ruixue Zhang, Jiawen Hao, Wenjun Jiang, Hongsheng Bi, Dadong Guo
Summary: This study aimed to investigate the effect of miR-138-5p on choroidal fibrosis in myopic guinea pigs via regulating the HIF-1 alpha signaling pathway. The results showed that miR-138-5p can efficiently decrease the refraction and ocular length, and ameliorate the choroidal fibrosis of the experimental myopic guinea pigs through inhibiting the HIF-1 alpha signaling pathway. These findings provide new insight into controlling myopic development using microRNAs in clinical practice.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jie Xu, Gabriel Nunez
Summary: The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated in response to cellular disturbances caused by infection and sterile injury. It triggers the release of inflammatory molecules and induces cell death. Understanding the structure and activation of NLRP3 inflammasome is important for studying inflammatory diseases.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Immunology
Kai Yang, Shuo Xu, Hongmei Zhao, Lingshuang Liu, Xiaofang Lv, Fang Hu, Lei Wang, Qiuxia Ji
Summary: The combination of hypoxia and P. gingivalis-LPS significantly enhances the activation of the NLRP3 inflammasome in human gingival fibroblasts, leading to an inflammatory response through high levels of interleukin-1? and GSDMD-mediated pyroptosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Environmental Sciences
Runxiao Zheng, Liming Wang, Xiaqing Wu, Panpan Song, Yanjing Wang, Haiyuan Zhang
Summary: The study found that insoluble La(III) species formed under physiological conditions can activate the NLRP3 inflammasome, leading to chronic toxicity, possibly due to K+ efflux and lysosomal rupture. Mice exposed to soluble La(III) species daily for 90 days showed activation of the NLRP3 inflammasome in liver and kidney, resulting in chronic fibrosis, which may be related to the formation of insoluble La(III) species.
ENVIRONMENTAL POLLUTION
(2021)
Review
Biochemistry & Molecular Biology
Laura Hurtado-Navarro, Diego Angosto-Bazarra, Pablo Pelegrin, Alberto Baroja-Mazo, Santiago Cuevas
Summary: Inflammasomes, particularly the NLRP3 inflammasome, play a crucial role in regulating inflammation and pyroptosis, a pro-inflammatory pathway involved in liver pathophysiology. Oxidative stress, inflammasome activation, and pyroptosis are interconnected molecular mechanisms contributing to the progression of liver diseases. Antioxidants that activate Nrf2 may have protective effects against liver inflammation and fibrosis. This review highlights the role of NLRP3 inflammasome and pyroptosis in various hepatic diseases and suggests the potential use of Nrf2 inducers as liver protective compounds.
