Article
Multidisciplinary Sciences
Hayley Muendlein, Wilson M. Connolly, Zoie Magri, David Jetton, Irina Smirnova, Alexei Degterev, Siddharth Balachandran, Alexander Poltorak
Summary: ZBP1 is known for its role in cell death, but it also promotes inflammatory responses to bacterial lipopolysaccharide or double-stranded RNA. ZBP1 facilitates the delivery and ubiquitination of RIPK1, sustaining the activation of inflammatory signaling cascades. This finding highlights the crucial role of ZBP1 in regulating both bacterial and viral responses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cardiac & Cardiovascular Systems
Alexander Maier, Yohana C. Toner, Jazz Munitz, Nathaniel A. T. Sullivan, Ken Sakurai, Anu E. Meerwaldt, Eliane E. S. Brechbuhl, Geoffrey Prevot, Yuri van Elsas, Rianne J. F. Maas, Anna Ranzenigo, Georgios Soultanidis, Mohammad Rashidian, Carlos Perez-Medina, Gyu Seong Heo, Robert J. Gropler, Yongjian Liu, Thomas Reiner, Matthias Nahrendorf, Filip K. Swirski, Gustav J. Strijkers, Abraham J. P. Teunissen, Claudia Calcagno, Zahi A. Fayad, Willem J. M. Mulder, Mandy M. T. van Leent
Summary: Research on atherosclerotic cardiovascular disease in the past 2 decades has identified inflammation as a major contributor to the disease process. This study developed and applied multiparametric imaging methods to investigate the immune response after myocardial infarction. The results demonstrated the strengths and capabilities of these imaging techniques in detecting inflammatory activity in cardiovascular disease.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Fengying Gao, Jicai Pang, Maixin Lu, Zhigang Liu, Miao Wang, Xiaoli Ke, Mengmeng Yi, Jianmeng Cao
Summary: OnTLR3 is broadly expressed in Nile tilapia and plays an important role in immune response, serving as a pattern recognition receptor in pathogen invasion.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Cell Biology
Milton Pereira, Danielle F. Durso, Clare E. Bryant, Evelyn A. Kurt-Jones, Neal Silverman, Douglas T. Golenbock, Ricardo T. Gazzinelli
Summary: This study examines the importance of IRAK proteins in TLR4 activation and confirms the essential role of IRAK4 kinase activity in MYD88 signaling. It also reveals the crucial role of the IRAK4 scaffold in integrating MYD88 and TRIF in TLR4 signaling.
Article
Neurosciences
Luca Ghita, Veronika Breitkopf, Felix Mulenge, Andreas Pavlou, Olivia Luise Gern, Veronica Duran, Chittappen Kandiyil Prajeeth, Moritz Kohls, Klaus Jung, Martin Stangel, Imke Steffen, Ulrich Kalinke
Summary: In TBEV-infected mice, astrocytes are important producers of IFN-beta, showing biphasic induction that depends on MAVS initially and later on MyD88/TRIF signaling. Astrocytes play a crucial role in early anti-viral responses, while MAVS deficiency negatively affects this response, resulting in increased TBEV replication. Treatment with inhibiting peptides can reduce late IFN-beta responses in WT astrocytes and block entirely IFN-beta responses in MAVS-deficient astrocytes after TBEV exposure.
JOURNAL OF NEUROSCIENCE RESEARCH
(2021)
Article
Microbiology
Quan Zeng, Jiaqi Liu, Zhaoyang Li, Yucan Zhang, Shaopo Zu, Xueyan Ding, Honglei Zhang
Summary: This study demonstrates that the nonstructural protein 4B (NS4B) of Japanese encephalitis virus (JEV) suppresses interferon-beta production by targeting TLR3 and TRIF proteins, thereby interfering with the host's antiviral response.
VETERINARY MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Marinaliz Reynoso, Stuart Hobbs, Alexander L. L. Kolb, Ronald W. W. Matheny, Brandon M. M. Roberts
Summary: Macrophages are important for the response to infection and/or tissue repair. In this study, the NF-kappa B pathway in response to an inflammatory stimulus was examined using different types of macrophages. The results show that MyD88 knockout decreases the signaling of NF-kappa B, and partial restoration of cytokine secretion is observed with partial expression of MyD88.
Article
Fisheries
Tan Phat Nguyen, Bao Trung Nguyen, Fan-Hua Nan, Meng-Chou Lee, Po-Tsang Lee
Summary: Nile tilapia (Oreochromis niloticus) is an important food fish species mainly cultivated in tropical and subtropical countries. This study focuses on Toll-like receptors (TLRs) and the clonation of OnTLR23 in fish cells. The study also explores the interaction of OnTLR23 with other molecules and its potential role in immune responses.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Article
Fisheries
Nguyen Bao Trung, Fan-Hua Nan, Meng-Chou Lee, Jiun-Yan Loh, Hong-Yi Gong, Ming-Wei Lu, Ho Thi Hang, Yu-Lin Lin, Po-Tsang Lee
Summary: TLR18 is expressed in all tissues, with the highest levels in the intestine and the lowest in the liver. It is up-regulated in immune-related organs after bacterial and poly I:C challenges, and in THK cells after LPS stimulation. TLR18 localizes in the intracellular compartment, and interacts with MyD88 and TRIF as adaptors. Constitutively active TLR18 induces the production of various effectors like cytokines and antimicrobial peptides in THK cells.
FISH & SHELLFISH IMMUNOLOGY
(2021)
Article
Oncology
Du-Jiang Yang, Xiao-Dong Wang, Xiao-Ying Fu, Hui-Min Lu, Zong-Guang Zhou, Yong Liu
Summary: The study investigated the potential role of MyD88 in the pathogenesis of acute pancreatitis. Deletion of MyD88 resulted in more severe acute experimental pancreatitis, with increased amylase and lipase activities, pancreatic MPO activity, reduced anti-inflammatory response, reduced apoptosis, and increased necrosis. The study suggests that MyD88 represents a potential therapeutic target in the management of acute pancreatitis.
ANNALS OF TRANSLATIONAL MEDICINE
(2022)
Article
Immunology
Junjie Zhou, Xihe Qin, Li Li, Dan Tian, Zhimin Zou, Zhengtao Gu, Lei Su
Summary: This study aimed to investigate the mechanism of heat-induced intestinal epithelial cell death. The results showed that heat stress upregulated TLR3 and facilitated the formation of TRIF-RIP3 complex, which activated the RIP3-MLKL signaling pathway, leading to necroptosis in intestinal epithelial cells. In addition, heat stress promoted the phosphorylation of p53 and increased TLR3 expression. Thus, heat stress induced necroptosis in intestinal epithelial cells through the p53-TLR3-TRIF-RIP3-MLKL signaling pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Plant Sciences
Yue Li, Lei Zhang, Pan Ren, Yang Yang, Sinai Li, Xiaomei Qin, Meng Zhang, Mingxue Zhou, Weihong Liu
Summary: Our study demonstrates that Qing-Xue-Xiao-Zhi formula (QXXZF) has a significant inhibitory effect on the development of atherosclerosis in ApoE(-/-) mice fed a high-fat and high-choline diet, with decreased atherosclerotic plaques, plasma lipid levels, and serum TMAO content. Additionally, QXXZF effectively reduces foam cell formation and promotes reverse cholesterol transport in macrophages, influencing cholesterol metabolism by inhibiting the TLR4-mediated NF-kappa B axis. These findings provide new insights into the anti-atherosclerotic mechanisms of QXXZF.
Article
Food Science & Technology
Xiangfu Gu, Jiaqi Tang, Yue Zhao, Chuhong Su, Lingyu Xiao, Huiyu Luo, Yuguo Liu, Fei Xiong, Zhongdaixi Zheng, Junbin Chen, Longying Zha
Summary: The study shows that SS-A(1) inhibits inflammation by regulating the lipid raft-mediated TLR4 signaling, affecting the recruitment and dimerization of TLR4 by maintaining cholesterol homeostasis.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Hematology
Marco Busnelli, Stefano Manzini, Matteo Chiara, Alice Colombo, Fabrizio Fontana, Roberto Oleari, Francesco Poti, David Horner, Stefano Bellosta, Giulia Chiesa
Summary: The study found that overexpression of ApoA-I in EKO mice aorta modulates the development of atherosclerosis, affecting pathways beyond those associated with inflammation and immune response.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Wu Luo, Ke Lin, Junyi Hua, Jibo Han, Qiuyan Zhang, Lingfeng Chen, Zia A. Khan, Gaojun Wu, Yi Wang, Guang Liang
Summary: Diabetes-induced chronic inflammation contributes to the development of diabetic cardiomyopathy (DCM). This study investigates the pharmacological effects and mechanisms of Schisandrin B (Sch B), a natural anti-inflammatory compound, against DCM. Results show that Sch B protects against high glucose-induced hypertrophy and fibrosis in cultured cardiomyocytes via MyD88-dependent inflammatory gene expression. Sch B inhibits MyD88 activation and does not affect MyD88-independent Toll-like receptor signaling. In mouse models, Sch B treatment improves heart function, reduces myocardial injuries, and decreases inflammatory cytokine secretion. Cardiomyocyte-specific MyD88 knockout also protects against cardiac inflammation and injury in diabetic mice. Overall, this study highlights the importance of MyD88 in DCM and the potential of Sch B as a therapeutic target for reducing inflammation in DCM.
Editorial Material
Endocrinology & Metabolism
Lale Ozcan, Devram S. Ghorpade, Ira Tabas
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Medicine, Research & Experimental
Matthew DeBerge, Kristofor Glinton, Manikandan Subramanian, Lisa D. Wilsbacher, Carla Rothlin, Ira Tabas, Edward B. Thorp
Summary: In response to myocardial ischemia/reperfusion injury, AXL receptor in myeloid cells plays a maladaptive role leading to increased inflammation, adverse ventricular remodeling, and impaired contractile function. Inhibiting AXL alone can improve cardiac healing, and combination with blocking MerTK cleavage enhances the efficacy further, suggesting macrophage TAM receptors as potential therapeutic targets for myocardial infarction.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Medicine, Research & Experimental
Canan Kasikara, Maaike Schilperoort, Brennan Gerlach, Chenyi Xue, Xiaobo Wang, Ze Zheng, George Kuriakose, Bernhard Dorweiler, Hanrui Zhang, Gabrielle Fredman, Danish Saleheen, Muredach P. Reilly, Ira Tabas
Summary: The rs9349379-G allele is associated with lower levels of PHACTR1 and impaired efferocytosis in macrophages, potentially contributing to CAD risk by compromising the clearance of apoptotic cells in atherosclerotic lesions.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Multidisciplinary Sciences
Lale Ozcan, Canan Kasikara, Arif Yurdagul, George Kuriakose, Brian Hubbard, Michael H. Serrano-Wu, Ira Tabas
Summary: The study found that two novel MK2 inhibitors, TBX-1 and TBX-2, can improve glucose metabolism, lower plasma cholesterol and triglyceride levels, and reduce lesion area, plaque necrosis, and increase fibrous cap thickness in high-fat Western diet-fed mice.
Article
Biochemical Research Methods
Xiangang Huang, Chuang Liu, Na Kong, Yufen Xiao, Arif Yurdagul, Ira Tabas, Wei Tao
Summary: Macrophages play a role in promoting plaque progression in atherosclerosis and are an attractive therapeutic target. Researchers have developed siRNA nanoparticles that can silence CaMKII γ activity in macrophages for the treatment of atherosclerosis.
Review
Cardiac & Cardiovascular Systems
Wei Chen, Maaike Schilperoort, Yihai Cao, Jinjun Shi, Ira Tabas, Wei Tao
Summary: Nanotechnology has the potential to improve our understanding of the pathophysiology of atherosclerosis and contribute to the development of novel diagnostic and therapeutic strategies. Targeted nanoparticles for macrophages offer more precise imaging and treatment methods. Future directions include accelerating the clinical translation of nanomedicine for the treatment of atherosclerosis.
NATURE REVIEWS CARDIOLOGY
(2022)
Article
Cell Biology
Ingmar Mederacke, Aveline Filliol, Silvia Affo, Ajay Nair, Celine Hernandez, Qiuyan Sun, Florian Hamberger, Francesco Brundu, Yu Chen, Aashreya Ravichandra, Peter Huebener, Helena Anke, Hongxue Shi, Raquel A. Martinez Garcia de la Torre, James R. Smith, Neil C. Henderson, Florian W. R. Vondran, Carla Rothlin, Heike Baehre, Ira Tabas, Pau Sancho-Bru, Robert F. Schwabe
Summary: The study identifies P2Y14 ligands and receptors as a profibrogenic DAMP pathway that directly links cell death to fibrogenesis.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Aveline Filliol, Yoshinobu Saito, Ajay Nair, Dianne H. Dapito, Le-Xing Yu, Aashreya Ravichandra, Sonakshi Bhattacharjee, Silvia Affo, Naoto Fujiwara, Hua Su, Qiuyan Sun, Thomas M. Savage, John R. Wilson-Kanamori, Jorge M. Caviglia, LiKang Chin, Dongning Chen, Xiaobo Wang, Stefano Caruso, Jin Ku Kang, Amit Dipak Amin, Sebastian Wallace, Ross Dobie, Deqi Yin, Oscar M. Rodriguez-Fiallos, Chuan Yin, Adam Mehal, Benjamin Izar, Richard A. Friedman, Rebecca G. Wells, Utpal B. Pajvani, Yujin Hoshida, Helen E. Remotti, Nicholas Arpaia, Jessica Zucman-Rossi, Michael Karin, Neil C. Henderson, Ira Tabas, Robert F. Schwabe
Summary: The shift in HSC subpopulations during chronic liver disease is associated with a switch from HCC protection to promotion. Quiescent and cytokine-producing HSCs prevent hepatocyte death and HCC development, while activated myofibroblastic HSCs promote proliferation and tumor development through increased stiffness and TAZ and discoidin domain receptor 1 activation.
Article
Cell Biology
Hongxue Shi, Xiaobo Wang, Fang Li, Brennan D. Gerlach, Arif Yurdagul, Mary P. Moore, Sharon Zeldin, Hanrui Zhang, Bishuang Cai, Ze Zheng, Luca Valenti, Ira Tabas
Summary: Impaired clearance of necroptotic hepatocytes (necHCs) by liver macrophages due to up-regulation of the CD47-SIRP alpha axis contributes to fibrotic nonalcoholic steatohepatitis (NASH). Therapeutic blockade of the CD47-SIRP alpha axis may decrease the accumulation of necHCs in NASH liver and dampen the progression of hepatic fibrosis.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Jianting Shi, Xun Wu, Ziyi Wang, Fang Li, Yujiao Meng, Rebecca M. Moore, Jian Cui, Chenyi Xue, Katherine R. Croce, Arif Yurdagul, John G. Doench, Wei Li, Konstantinos S. Zarbalis, Ira Tabas, Ai Yamamoto, Hanrui Zhang
Summary: This study identified WDFY3 as a novel regulator of efferocytosis through a genome-wide CRISPR screen, revealing its role in promoting LC3 lipidation and lysosomal acidification for the degradation of apoptotic cell components.
NATURE COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Yoshinobu Saito, Dingzi Yin, Naoto Kubota, Xiaobo Wang, Aveline Filliol, Helen Remotti, Ajay Nair, Ladan Fazlollahi, Yujin Hoshida, Ira Tabas, Kirk J. Wangensteen, Robert F. Schwabe
Summary: This study investigated the regulation and function of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in hepatocellular carcinoma (HCC). The results showed that TAZ expression was regulated by cholesterol synthesis and that it promoted HCC growth through increased tumor cell proliferation. The cholesterol-TAZ-TEAD2-ANLN/KIF23 pathway was identified as a mediator of HCC proliferation and a potential therapeutic target, which could be combined with tumor immune micro-environment (TIME)-targeted therapies.
Review
Immunology
Maaike Schilperoort, David Ngai, Santosh R. Sukka, Kleopatra Avrampou, Hongxue Shi, Ira Tabas
Summary: The process of macrophages engulfing dying cells, known as efferocytosis, is tightly regulated and involves sensing, binding, engulfment, and digestion of apoptotic cells. Efferocytosis not only prevents tissue necrosis and inflammation caused by secondary necrosis of dying cells, but also promotes pro-resolving signaling in macrophages, which is essential for tissue resolution and repair following injury or inflammation. The cargo released from apoptotic cells after their engulfment and digestion by macrophages, containing amino acids, nucleotides, fatty acids, and cholesterol, plays a crucial role in this pro-resolving reprogramming.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Endocrinology & Metabolism
Maaike Schilperoort, David Ngai, Marina Katerelos, David A. Power, Ira Tabas
Summary: The study reveals that transient increase in glycolysis and lactate production are essential for continual efferocytosis, contrasting with prolonged glycolysis in pro-inflammatory macrophages. This unique metabolic process depends on the activation of PFKFB2 enzyme and promotes continual efferocytosis through lactate-mediated upregulation of MerTK and LRP1. Inhibiting this process may provide a potential therapeutic pathway in chronic inflammatory diseases.
Article
Gastroenterology & Hepatology
Mary Patricia Moore, Xiaobo Wang, Hongxue Shi, Marica Meroni, Alessandro Cherubini, Luisa Ronzoni, Elizabeth J. Parks, Jamal A. Ibdah, R. Scott Rector, Luca Valenti, Paola Dongiovanni, Ira Tabas
Summary: Circulating IHH is associated with the development and progression of NASH and liver fibrosis, making it a potential mechanism-based biomarker to evaluate NASH therapies.
Article
Endocrinology & Metabolism
Patrick B. Ampomah, Bishuang Cai, Santosh R. Sukka, Brennan D. Gerlach, Arif Yurdagul, Xiaobo Wang, George Kuriakose, Lancia N. F. Darville, Yan Sun, Simone Sidoli, John M. Koomen, Alan R. Tall, Ira Tabas
Summary: This study demonstrates that methionine derived from apoptotic cells taken up by macrophages during efferocytosis plays a role in mediating tissue resolution by providing a substrate for DNA methylation and repressing the expression of the ERK1/2 phosphatase Dusp4, leading to activation of ERK1/2 and the expression of pro-resolving mediators.
Article
Biochemistry & Molecular Biology
Binbin Chang, Zhang Wang, Hui Cheng, Tingyuan Xu, Jieyu Chen, Wan Wu, Yizhi Li, Yong Zhang
Summary: Acacetin can attenuate sepsis-induced ALI by inhibiting the inflammatory response and promoting macrophage polarization. This study is of great significance for the development of new treatments for sepsis-induced ALI.
Review
Biochemistry & Molecular Biology
Nikoleta Bizymi, Andreas M. Matthaiou, Irene Mavroudi, Aristea Batsali, Helen A. Papadaki
Summary: Myeloid-derived suppressor cells (MDSCs) are innate immune cells that have immunomodulatory properties. They interact extensively with other innate or adaptive immune cells and can either enhance or attenuate immune responses depending on the triggering conditions. However, their positive role in host defense mechanisms is rarely discussed in the literature.