Article
Environmental Sciences
Chenyang Han, Hongyan Pei, Yongjia Sheng, Jin Wang, Xiaohong Zhou, Wenyan Li, Li Guo, Yun Kong, Yi Yang
Summary: In this study, it was found that triptolide (TRI) induces liver injury primarily through the Caspase-3-GSDME pyroptosis signal. TRI can promote Caspase-3 maturation and regulate kupffer cell pyroptosis. These findings provide a new perspective for the safe use of TRI.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Pharmacology & Pharmacy
Yang-Yang Zhao, Dong-Ming Wu, Miao He, Feng Zhang, Ting Zhang, Teng Liu, Jin Li, Li Li, Ying Xu
Summary: This study identified a novel drug, samotolisib (ST), which inhibited caspase-11 and GSDMD-NT activation and improved liver injury in patients with sepsis by regulating the PI3K/AKT/mTOR/Nedd4 signaling pathway.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Huairui Shi, Yang Gao, Zhen Dong, Ji'e Yang, Rifeng Gao, Xiao Li, Shuqi Zhang, Leilei Ma, Xiaolei Sun, Zeng Wang, Feng Zhang, Kai Hu, Aijun Sun, Junbo Ge
Summary: The study demonstrates the significant role of GSDMD-mediated cardiomyocyte pyroptosis in myocardial I/R injury, and suggests that the caspase-11/GSDMD pathway may be essential to this process. Furthermore, GSDMD inhibition significantly reduces cardiomyocyte pyroptosis and I/R-induced myocardial injury.
CIRCULATION RESEARCH
(2021)
Review
Immunology
Chaoze Jiao, Haidan Zhang, Hongyao Li, Xu Fu, Yujie Lin, Chenglong Cao, Shixian Liu, Yijing Liu, Peiwu Li
Summary: The inflammatory response helps combat pathogens, but excessive inflammation in sepsis can cause tissue and organ damage. Pyroptosis, a form of programmed cell death executed by the GSDMs family, has been identified as a crucial component of the sepsis mechanism. While previous research has focused on one pathway, there is a lack of study on other GSDMs family members in sepsis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Immunology
Ping Jiang, Hongzhi Chen, Xiaojing Feng, Huiqi Xie, Mengjie Jiang, Danning Xu, Haoneng Tang, Ningjie Zhang, Jianlin Chen, Lei Zhang, Lingli Tang
Summary: We found that C. trachomatis L2 infection induced pyroptosis in mouse macrophages, which was accompanied by activation of caspase-1 and caspase-11 as well as gasdermin D (GSDMD) activation. Inhibition of these inflammatory caspases suppressed GSDMD activation. Importantly, the pyroptosis response significantly inhibited the intracellular growth of C. trachomatis, suggesting it can be utilized as an intrinsic mechanism to restrict C. trachomatis infection.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Wen Li, Jing Sun, Xiaoxi Zhou, Yue Lu, Wenpeng Cui, Lining Miao
Summary: Pyroptosis is a lytic programmed cell death that plays a crucial role in diabetic complications. Research has identified various signaling pathways associated with pyroptosis, and explored the potential value of pyroptosis inhibitors in the treatment of diabetic nephropathy.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Gastroenterology & Hepatology
Yingwei Zhu, Han Zhao, Jian Lu, Kai Lin, Jingbin Ni, Gaojue Wu, Hong Tang
Summary: The study found that caspase-11 was upregulated in the livers of NASH mice. Caspase-11-deficient mice treated with MCD showed significantly reduced liver injury, fibrosis, and inflammation, as well as inhibited activation of gasdermin D and interleukin-1 beta. Overexpression of caspase-11 promoted steatohepatitis, indicating that caspase-11-mediated hepatocytic pyroptosis promotes the progression of NASH.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Pharmacology & Pharmacy
Mengwei Zhang, Guofeng Xu, Xin Zhou, Xing Wang, Zhibin Wang, Hongmei Tang, Xiaoyun Wang, Yuejiao Li, Xiefang Yuan, Yuying Li
Summary: This study demonstrates that bone marrow-derived mesenchymal stem cells (BMMSCs) can prevent and ameliorate acute lung injury (ALI) by inhibiting apoptosis and cytokine storm in lung cells. In vitro and in vivo experiments support these findings and suggest that MA01-induced apoptosis is associated with the BAK/BAX-dependent mitochondrial apoptosis pathway.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Vasantha L. Kolachala, Chrissy Lopez, Ming Shen, Dmitry Shayakhmetov, Nitika Arora Gupta
Summary: The study identified Caspase 1 as a key driver of hepatocellular injury in steatotic liver undergoing ischemia reperfusion injury (IRI), with its inhibition leading to hepatoprotection, providing a new therapeutic target for treatment.
Article
Cell Biology
Omar Escobar-Chavarria, Alejandro Benitez-Guzman, Itzel Jimenez-Vazquez, Jacobo Carrisoza-Urbina, Lourdes Arriaga-Pizano, Sara Huerta-Yepez, Guillermina Baay-Guzman, Jose A. Gutierrez-Pabello
Summary: The necrotic cell death induced by Mycobacterium bovis and the inflammasome activation in bovine macrophages help control bacterial growth.
Article
Immunology
Wei Zhu, Yuan-Yuan Li, Han-Xu Zeng, Xue-Qi Liu, Yu-Ting Sun, Ling Jiang, Ling-Ling Xia, Yong-Gui Wu
Summary: The study demonstrates the protective effects of carnosine on glomerular podocytes in diabetic nephropathy, highlighting its potential as a therapeutic agent by targeting caspase-1. The mechanism involves inhibition of podocyte pyroptosis and inflammation, with promising results in both in vivo and in vitro models. This novel role of carnosine in alleviating podocyte injury provides new insights for potential treatment of diabetic nephropathy.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Immunology
Li Wang, Xubin Dong, Shuyi Feng, Haoran Pan, Xuepei Jang, Lifei Chen, Yuan Zhao, Weizhen Chen, Zhiming Huang
Summary: In this study, the therapeutic effect of VX765 on colitis was investigated using a mouse model. The results showed that VX765 attenuated body weight loss, colonic shortening, and colonic pathological injury in mice. It was found that VX765 exerted its therapeutic effect by inhibiting pyroptosis and curbing the production of key inflammatory cytokines.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Skylar S. Wright, Swathy O. Vasudevan, Vijay A. Rathinam
Summary: The noncanonical inflammasome plays important roles in regulating cell death and inflammation by monitoring bacterial lipopolysaccharide in the cytosol. Recent studies have advanced our understanding of the activation mechanism and biological consequences of the noncanonical inflammasome, but there are still remaining gaps to be addressed.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Review
Immunology
Can Gan, Qiuyu Cai, Chengwei Tang, Jinhang Gao
Summary: This review summarizes the activation and function of inflammasome complexes and discusses the association between inflammasomes, pyroptosis, and liver fibrosis. Unlike other reviews, the author focuses on the effect of inflammasome activation in various liver cells during the development of liver fibrosis and highlights the latest progress of pharmacological intervention in inflammasome-mediated liver fibrosis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Environmental Sciences
Dan Zheng, Zhixiong Shi, Man Yang, Baolu Liang, Xianqing Zhou, Li Jing, Zhiwei Sun
Summary: DBDPE induces vascular endothelial injury in rats and human vascular endothelial cells, possibly by causing endothelial cell pyroptosis mediated by NLRP3 inflammasome.
Article
Rheumatology
Tomas Mustelin, Nunzio Bottini, Stephanie M. Stanford
ARTHRITIS & RHEUMATOLOGY
(2019)
Article
Hematology
Lise M. Lindahl, Andreas Willerslev-Olsen, Lise M. R. Gjerdrum, Pia R. Nielsen, Edda Blumel, Anne H. Rittig, Pamela Celis, Bjorn Herpers, Juergen C. Becker, Birgitte Stausbol-Gron, Mariusz A. Wasik, Maria Gluud, Simon Fredholm, Terkild B. Buus, Claus Johansen, Claudia Nastasi, Lukas Peiffer, Linda Kubat, Michael Bzorek, Jens O. Eriksen, Thorbjorn Krejsgaard, Charlotte M. Bonefeld, Carsten Geisler, Tomas Mustelin, Erik Langhoff, Michael Givskov, Anders Woetmann, Mogens Kilian, Thomas Litman, Lars Iversen, Niels Odum
Article
Rheumatology
Victoria Carter, John LaCava, Martin S. Taylor, Shu Ying Liang, Cecilia Mustelin, Kennedy C. Ukadike, Anders Bengtsson, Christian Lood, Tomas Mustelin
ARTHRITIS & RHEUMATOLOGY
(2020)
Review
Immunology
Tomas Mustelin, Christian Lood, Natalia V. Giltiay
FRONTIERS IN IMMUNOLOGY
(2019)
Letter
Rheumatology
Tomas Mustelin, Kennedy Ukadike, John LaCava, Marty Taylor
ARTHRITIS & RHEUMATOLOGY
(2020)
Article
Gastroenterology & Hepatology
Casey A. Rimland, Samantha G. Tilson, Carola M. Morell, Rute A. Tomaz, Wei-Yu Lu, Simone E. Adams, Nikitas Georgakopoulos, Francisco Otaizo-Carrasquero, Timothy G. Myers, John R. Ferdinand, Richard L. Gieseck, Fotios Sampaziotis, Olivia C. Tysoe, Alexander Ross, Judith M. Kraiczy, Brandon Wesley, Daniele Muraro, Matthias Zilbauer, Gabriel C. Oniscu, Nicholas R. F. Hannan, Stuart J. Forbes, Kourosh Saeb-Parsy, Thomas A. Wynn, Ludovic Vallier
Summary: Researchers successfully established organoids derived from human gallbladder, common bile duct, pancreatic duct, and IHBDs, expressing stem/progenitor and ductal markers, but conserving only limited regional-specific markers, with differences in response and expression of cell markers between IHBD and EHBD organoids.
Article
Immunology
Stefanie Y. Tan, Yogeshwar Kelkar, Angela Hadjipanayis, Arun Shipstone, Thomas A. Wynn, J. Perry Hall
JOURNAL OF IMMUNOLOGY
(2020)
Article
Pathology
Zaher A. Radi, Thomas A. Wynn
TOXICOLOGIC PATHOLOGY
(2020)
Review
Multidisciplinary Sciences
Neil C. Henderson, Florian Rieder, Thomas A. Wynn
Review
Medicine, General & Internal
Kennedy C. Ukadike, Tomas Mustelin
Summary: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a multifactorial etiology involving genetic, immunologic, hormonal, and environmental factors. The hypothesis proposes that L1 retrotransposons play a key role in SLE pathogenesis by activating type I interferon production and inducing immune responses similar to chronic viral infections. Understanding the role of L1 retroelements in SLE may lead to new diagnostic, prognostic, and therapeutic strategies for the disease.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Natalia Jaeger, Ramya Gamini, Marina Cella, Jorge L. Schettini, Mattia Bugatti, Shanrong Zhao, Charles V. Rosadini, Ekaterina Esaulova, Blanda Di Luccia, Baylee Kinnett, William Vermi, Maxim N. Artyomov, Thomas A. Wynn, Ramnik J. Xavier, Scott A. Jelinsky, Marco Colonna
Summary: Crohn's disease is a chronic transmural inflammation in the gut caused by dysregulated interaction between microbiome and gut immune system. Studies have shown that T cells from intestinal epithelium and lamina propria in CD patients exhibit unique subsets and altered phenotypes during inflammation.
NATURE COMMUNICATIONS
(2021)
Article
Rheumatology
Xiaoxing Wang, Amanda Hefton, Kathryn Ni, Kennedy C. Ukadike, Michael A. Bowen, Mary Eckert, Anne Stevens, Christian Lood, Tomas Mustelin
Summary: This study found that autoantibodies targeting the citrullinated epitopes on the HERV-K protein are present in patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), and are associated with pathogenic protein citrullination in RA.
JOURNAL OF RHEUMATOLOGY
(2022)
Article
Microbiology
Amanda Laine, Xiaoxing Wang, Kathryn Ni, Sarah E. B. Smith, Rayan Najjar, Leanne S. S. Whitmore, Michael M. Yacoub, Alison Bays, Michael Gale, Tomas Mustelin
Summary: Many patients with autoimmune diseases have autoantibodies against proteins encoded by genomic retroelements, suggesting a lack of immune tolerance. In this study, the researchers found that transmembrane envelope (Env) protein encoded by HERV-K102 is increased in rheumatoid arthritis (RA) patients, while HERV-K108 expression is higher in other immune cells. Patient autoantibodies recognized endogenously expressed Env in breast cancer cells and RA neutrophils. The findings suggest that HERV-K102 is the main contributor to cell surface Env on neutrophils in RA.
Article
Rheumatology
Kennedy C. Ukadike, Kathryn Ni, Xiaoxing Wang, Martin S. Taylor, John LaCava, Lauren M. Pachman, Mary Eckert, Anne Stevens, Christian Lood, Tomas Mustelin
Summary: In this study, it was found that children with active SLE have elevated IgG and IgA autoantibodies against L1 p40. The p40 protein was detected in circulating granulocytes in pediatric and adult SLE patients, and autoantibody levels correlated with disease activity. Markers of neutrophil activation and death also correlated with anti-p40 autoantibodies and disease activity, suggesting neutrophils play a role in the production of p40 in SLE.
ARTHRITIS RESEARCH & THERAPY
(2021)
Article
Immunology
Amanda Hefton, Shu Ying Liang, Kathryn Ni, Victoria Carter, Kennedy Ukadike, Christian Lood, Tomas Mustelin
JOURNAL OF TRANSLATIONAL AUTOIMMUNITY
(2019)