Article
Multidisciplinary Sciences
Lijing Su, Muhammad Athamna, Ying Wang, Junmei Wang, Marina Freudenberg, Tao Yue, Jianhui Wang, Eva Marie Y. Moresco, Haoming He, Tsaffrir Zor, Bruce Beutler
Summary: Sulfatides can activate mouse immune responses via the TLR4-MD-2 complex, but exhibit antagonistic effects in human cells. Their activity is related to the presence of the sulfate group and the length of the fatty acid chain, and their structure mimics the activation mechanism of molecules like LPS in receptors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cell Biology
Wangrui Lei, Liyuan Jia, Zheng Wang, Zhenxing Liang, Zhao Aizhen, Yanqing Liu, Ye Tian, Lin Zhao, Yawu Chen, Guangyong Shi, Zhi Yang, Yang Yang, Xuezeng Xu
Summary: Fibrosis is an excessive self-repair response in the aging process of various organs. It is necessary to develop therapeutic strategies to restore tissue architecture without side effects. Chemokines play a crucial role in controlling the pathological processes involved in fibrosis, including inflammation, endothelial cell injury, and macrophage recruitment.
AGEING RESEARCH REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Haein Lee, Eunha Kim, Seyun Kim
Summary: In response to LPS stimulation, the levels of IPMK in macrophages decrease due to the binding of miR-181c to the 3'UTR of IPMK mRNA, which leads to the suppression of TLR4 signaling and inflammation. Deletion of the miR-181c-binding site prevents the downregulation of IPMK levels and reduces the activation of TRAF6 and the expression of proinflammatory cytokines.
Article
Biochemistry & Molecular Biology
Hiroyoshi Machida, Sumito Inoue, Akira Igarashi, Shinichi Saitoh, Keiko Yamauchi, Michiko Nishiwaki, Takako Nemoto, Yoichiro Otaki, Masamichi Sato, Kento Sato, Hiroshi Nakano, Sujeong Yang, Kodai Furuyama, Hiroaki Murano, Yu Ishibashi, Takahito Ota, Takashi Nakayama, Yoko Shibata, Masafumi Watanabe
Summary: The production of CCL17 by lung epithelial cells upon cigarette smoke exposure contributes to the accumulation of alveolar macrophages and the development of pulmonary emphysema. CCL17-induced production of CCL2 by macrophages plays a role in macrophage accumulation. These findings provide new insights into the pathogenesis of COPD.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Fisheries
Qiang Fu, Jie Hu, Pei Zhang, Yuqing Li, Shoucong Zhao, Min Cao, Ning Yang, Chao Li
Summary: Seventeen CC and CXC chemokine genes were identified in the turbot genome, making it a valuable resource for comparative immunological studies and functional characterization of chemokines in teleost.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Article
Immunology
Liangfei Niu, Geyang Luo, Rui Liang, Chenli Qiu, Jianwei Yang, Lingling Xie, Kaile Zhang, Yu Tian, Decheng Wang, Shu Song, Howard E. Takiff, Ka-Wing Wong, Xiaoyong Fan, Qian Gao, Bo Yan
Summary: This study reveals the important role of nlrc3-like in the regulation of macrophage homeostasis, early bacterial burden control, and inflammation response. Overexpression or deficiency of nlrc3-like leads to abnormal inflammation response and bacterial burden, highlighting the importance of balanced innate immune response during mycobacterial infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Xia Li, Meng Feng, Yanqing Zhao, Yuhan Zhang, Ruixue Zhou, Hang Zhou, Zhen Pang, Hiroshi Tachibana, Xunjia Cheng
Summary: Macrophages play a crucial role in combating amoebiasis by releasing pro-inflammatory cytokines in response to infection. Entamoeba histolytica can activate the NLRP3 inflammasome through secretion of peroxiredoxins during interaction with host cells, potentially offering a novel therapeutic approach for this global threat.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Sara Francisco, Jean-Marc Billod, Javier Merino, Carmen Punzon, Alicia Gallego, Alicia Arranz, Sonsoles Martin-Santamaria, Manuel Fresno
Summary: This study reveals that Ochrobactrum intermedium LPS can activate both TLR4 and TLR2, indicating the occurrence of TLR4/TLR2 heterodimerization, and the core saccharide plays an important role in this interaction.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Cong Lin, Hongshuang Wang, Miyuan Zhang, Sanam Mustafa, Yibo Wang, Hongyuan Li, Hang Yin, Mark R. Hutchinson, Xiaohui Wang
Summary: Biased pharmacological modulators offer potential therapeutic benefits by targeting specific receptors with increased efficiency and reduced adverse effects. While biased signaling modulators targeting GPCRs have received attention, the modulation of non-GPCR receptors remains to be explored, including Toll-like receptor 4 (TLR4). Discovery of biased modulators of TLR4 not only provides insights for future development but also potential drug candidates for other non-GPCR receptors.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Chemistry, Organic
Rachid Naitaleb, Agnes Denys, Fabrice Allain, Jerome Ausseil, Sylvestre Toumieux, Jose Kovensky
Summary: The study designed and synthesized sulfated compounds capable of crossing the blood-brain barrier, which were tested on HEK-TLR4 cells, demonstrating the potential of small oligosaccharides to modulate TLR4 activity with the 6-sulfate groups playing a key role in triggering TLR4 signalization.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Rebecca Heinz, Ulf C. Schneider
Summary: Subarachnoid hemorrhage can lead to severe neurological deficits for survivors. Secondary brain injury, primarily caused by cerebral inflammation after bleeding, can result in additional brain damage. The toll-like receptor (TLR)4 signaling pathway plays a critical role in the pathophysiology of acute brain injuries like subarachnoid hemorrhage (SAH).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Xinnan Gu, Mengjuan Wei, Feifei Hu, Hao Ouyang, Zhenlin Huang, Bin Lu, Lili Ji
Summary: In this study, it was found that chlorogenic acid (CGA) effectively improved non-alcoholic steatohepatitis (NASH) by inhibiting hepatic inflammation. CGA alleviated liver oxidative injury by activating nuclear factor erythroid 2-related factor 2 (Nrf2) and reduced liver steatosis by up-regulating peroxisome proliferator-activated receptor-alpha (PPAR alpha). Furthermore, CGA blocked the LPS-TLR4-MyD88 signaling pathway and attenuated hepatic inflammation.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Medicine, Research & Experimental
Sebastian J. Theobald, Alexander Simonis, Theodoros Georgomanolis, Christoph Kreer, Matthias Zehner, Hannah S. Eisfeld, Marie-Christine Albert, Jason Chhen, Susanne Motameny, Florian Erger, Julia Fischer, Jakob J. Malin, Jessica Graeb, Sandra Winter, Andromachi Pouikli, Friederike David, Boris Boell, Philipp Koehler, Kanika Vanshylla, Henning Gruell, Isabelle Suarez, Michael Hallek, Gerd Faetkenheuer, Norma Jung, Oliver A. Cornely, Clara Lehmann, Peter Tessarz, Janine Altmueller, Peter Nuernberg, Hamid Kashkar, Florian Klein, Manuel Koch, Jan Rybniker
Summary: Our study reveals that the SARS-CoV-2 spike protein induces inflammasome formation and IL-1 beta release in macrophages from COVID-19 patients, but not in healthy individuals. Furthermore, macrophages isolated from convalescent COVID-19 patients show robust S-protein-driven inflammasome activation, indicating innate immune memory after recovery.
EMBO MOLECULAR MEDICINE
(2021)
Article
Cell Biology
Shuhua Luo, Chaoxiong Liao, Lina Zhang, Chunxiu Ling, Xuedi Zhang, Pengyun Xie, Guomei Su, Zhanghui Chen, Liangqing Zhang, Tianwen Lai, Jing Tang
Summary: N6-methyladenosine (m6A) modification is the most prevalent mRNA internal modification and serves as a widespread regulatory mechanism in various physiological processes. In this study, we found that methyltransferase-like protein 3 (METTL3) plays a crucial role in neutrophil activation. METTL3 controls the release of neutrophils from the bone marrow to circulation by regulating the surface expression of CXC chemokine receptor 2 (CXCR2) through Toll-like receptor 4 (TLR4) signaling in lipopolysaccharide (LPS)-induced endotoxemia. We discovered that the mRNA of TLR4 is modified by m6A, resulting in increased translation and decreased degradation, leading to elevated levels of TLR4 protein and subsequent activation of TLR4 signaling in neutrophils. The downregulation of TLR4 expression reduces cytokine secretion in METTL3-deleted neutrophils upon LPS stimulation through the TLR4/Myd88/nuclear factor KB (NF-KB) signaling pathway. Overall, these findings demonstrate that METTL3-mediated TLR4 expression is a critical determinant of neutrophil activation in endotoxemia.
Article
Immunology
Pedro Paulo Carneiro, Andreza S. Dorea, Walker N. Oliveira, Luiz Henrique Guimaraes, Claudia Brodskyn, Edgar M. Carvalho, Olivia Bacellar
Summary: Research has shown that the use of TLR2 and TLR4 antagonists can reduce the number of infected cells and internalized parasites in monocytes of CL patients, as well as decrease oxidative burst, IL-1 beta, TNF, and CXCL9 production. Additionally, TNF production in cells from CL lesions also decreased after neutralization of TLR2 and TLR4.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Qinglan Wang, So Yeon Kim, Hiroshi Matsushita, Zhijun Wang, Vijay Pandyarajan, Michitaka Matsuda, Koichiro Ohashi, Takashi Tsuchiya, Yoon Seok Roh, Calvin Kiani, Yutong Zhao, Michael Chan, Suzanne Devkota, Shelly C. Lu, Tomoko Hayashi, Dennis A. Carson, Ekihiro Seki
Summary: TLR7 signaling has a protective effect in the AH mouse model, and the TLR7 agonistic agent 1Z1 holds therapeutic potential for the treatment of ALD. Oral administration of 1Z1 prevents intestinal barrier disruption and bacterial translocation, suppressing ethanol-induced hepatic injury, steatosis, and inflammation. 1Z1 treatment also up-regulates the expression of antimicrobial peptides and intestinal IL-22, modulating the microbiome composition and playing a protective role in the AH mouse model.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Editorial Material
Cell Biology
Yoon Mee Yang, Ekihiro Seki
Summary: The study shows that intracellular ER stress can be transmitted to neighboring hepatocytes through connexin 43, leading to exacerbated ER stress and promoting hepatosteatosis and insulin resistance.
Article
Oncology
Silvia Affo, Ajay Nair, Francesco Brundu, Aashreya Ravichandra, Sonakshi Bhattacharjee, Michitaka Matsuda, LiKang Chin, Aveline Filliol, Wen Wen, Xinhua Song, Aubrianna Decker, Jeremy Worley, Jorge Matias Caviglia, Lexing Yu, Deqi Yin, Yoshinobu Saito, Thomas Savage, Rebecca G. Wells, Matthias Mack, Lars Zender, Nicholas Arpaia, Helen E. Remotti, Raul Rabadan, Peter Sims, Anne-Laure Leblond, Achim Weber, Marc-Oliver Riener, Brent R. Stockwell, Jellert Gaublomme, Josep M. Llovet, Raghu Kalluri, George K. Michalopoulos, Ekihiro Seki, Daniela Sia, Xin Chen, Andrea Califano, Robert F. Schwabe
Summary: The study reveals that hepatic stellate cells (HSC) are the main source of cancer-associated fibroblasts (CAF), and HSC-derived CAF interact predominantly with tumor cells. In mouse models, CAF promote the progression of intrahepatic cholangiocarcinoma (ICC), while in patients, a high pan-CAF signature is associated with decreased survival and increased recurrence. Single-cell RNA sequencing segregates CAF into distinct subpopulations, with different interactions with tumor cells and promoting ICC growth.
Article
Multidisciplinary Sciences
Lucia Barbier-Torres, Ben Murray, Jin Won Yang, Jiaohong Wang, Michitaka Matsuda, Aaron Robinson, Aleksandra Binek, Wei Fan, David Fernandez-Ramos, Fernando Lopitz-Otsoa, Maria Luque-Urbano, Oscar Millet, Nirmala Mavila, Hui Peng, Komal Ramani, Roberta Gottlieb, Zhaoli Sun, Suthat Liangpunsakul, Ekihiro Seki, Jennifer E. Van Eyk, Jose M. Mato, Shelly C. Lu
Summary: MAT alpha 1 plays a role in reducing activity and causing mitochondrial dysfunction in alcohol-associated liver disease (ALD). This study found that the peptidyl-prolyl cis/trans isomerase PIN1 and kinase CK2 mediate the selective depletion of mitochondrial MAT alpha 1 in ALD. Blocking the interaction between PIN1 and MAT alpha 1 increased mitochondrial levels of MAT alpha 1 and protected against alcohol-induced mitochondrial dysfunction and fat accumulation.
NATURE COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Guangyue Yang, Liping Zhuang, Tiantian Sun, Yee Hui Yeo, Le Tao, Wei Zhang, Wenting Ma, Liu Wu, Zongguo Yang, Yanqin Yang, Dongying Xue, Jie Zhang, Rilu Feng, Ebert P. Matthias, Steven Dooley, Ekihiro Seki, Ping Liu, Cheng Liu
Summary: By analyzing serum, tissue mRNA, and biopsy data, we found the potential of sGDNF as a novel noninvasive biomarker for predicting cirrhosis in chronic hepatitis B patients.
CANADIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Le Tao, Guangyue Yang, Tiantian Sun, Jie Tao, Chan Zhu, Huimin Yu, Yalan Cheng, Zongguo Yang, Mingyi Xu, Yuefeng Jiang, Wei Zhang, Zhiyi Wang, Wenting Ma, Liu Wu, Dongying Xue, Dongxue Wang, Wentao Yang, Yongjuan Zhao, Shane Horsefield, Bostjan Kobe, Zhe Zhang, Zongxiang Tang, Qigen Li, Qiwei Zhai, Steven Dooley, Ekihiro Seki, Ping Liu, Jianrong Xu, Hongzhuan Chen, Cheng Liu
Summary: This study discovered the presence of TRPV1 in hepatic stellate cells (HSCs) and investigated its function in this cell type and liver fibrosis. TRPV1's expression is associated with liver fibrosis and its antifibrotic properties are attributed to the prevention of HSC activation. This finding could be a potential therapeutic strategy against liver fibrosis.
JOURNAL OF HEPATOLOGY
(2023)
Editorial Material
Gastroenterology & Hepatology
Jieun Kim, Ekihiro Seki
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Cell Biology
Zhijun Wang, So Yeon Kim, Wei Tu, Jieun Kim, Alexander Xu, Yoon Mee Yang, Michitaka Matsuda, Lien Reolizo, Takashi Tsuchiya, Sandrine Billet, Alexandra Gangi, Mazen Noureddin, Ben A. Falk, Sungjin Kim, Wei Fan, Mourad Tighiouart, Sungyong You, Michael S. Lewis, Stephen J. Pandol, Dolores Di Vizio, Akil Merchant, Edwin M. Posadas, Neil A. Bhowmick, Shelly C. Lu, Ekihiro Seki
Summary: Liver metastasis is a major cause of death in colorectal cancer patients with fatty liver, but the underlying mechanism is unclear. Our study found that extracellular vesicles (EVs) derived from hepatocytes in fatty liver enhance the progression of CRC liver metastasis by promoting oncogenic Yes-associated protein (YAP) signaling and an immunosuppressive microenvironment. Fatty liver upregulates Rab27a expression, promoting EV production from hepatocytes. These EVs transfer YAP signaling-regulating microRNAs to cancer cells, augmenting YAP activity by suppressing LATS2.
Review
Gastroenterology & Hepatology
Young-Sun Lee, Ekihiro Seki
Summary: It is crucial to choose an appropriate liver fibrosis model based on the purpose of study and type of disease due to the varied development and progression of liver fibrosis according to its etiology. This review provides a summary and analysis of various in vivo and in vitro liver fibrosis models and their implications and limitations. Liver fibrosis is a common consequence of various chronic liver diseases, and understanding its pathophysiology and identifying potential therapeutic targets is essential as it can progress to advanced liver diseases. Despite numerous studies, the underlying mechanisms of liver fibrosis remain unclear.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Gastroenterology & Hepatology
Jieun Kim, Ekihiro Seki
Summary: Hyaluronan plays a critical role in liver fibrosis by serving as both a key component of the extracellular matrix and a functional signaling molecule. Understanding the regulatory mechanisms of its synthesis and degradation, as well as its pathophysiological effects, is important for therapeutic intervention in liver fibrosis.
HEPATOLOGY COMMUNICATIONS
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Wei Fan, Jiaohong Wang, Tony Wh Li, Ting Liu, Jose M. Mato, Ekihiro Seki, Heping Yang, Shelly C. Lu
Meeting Abstract
Gastroenterology & Hepatology
Feng Wang, Yoon-Seok Roh, Jin Lee, Jeong-Su Park, So Yeon Kim, Yoon Mee Yang, Ekihiro Seki
Meeting Abstract
Gastroenterology & Hepatology
Hwan Ma, Yoon-Seok Roh, Jin Lee, Jeong-Su Park, Feng Wang, Ekihiro Seki
Article
Biochemistry & Molecular Biology
Sun Myoung Kim, Ga Yeon Song, Aeri Shim, Jee Hyung Lee, Cheol Bin Eom, Cheng Liu, Yoon Mee Yang, Ekihiro Seki
Summary: Liver fibrosis is a disease characterized by excessive extracellular matrix deposition during wound healing after repeated liver injury. Recent research has identified hyaluronan synthase 2 (HAS2) as a driver of liver fibrosis and hepatic stellate cell (HSC) activation. This study reveals that miR-200c negatively regulates HAS2 and contributes to the development of acute liver injury and chronic liver inflammation. Additionally, hyaluronidase-2 (HYAL2) is found to be overexpressed in fibrotic livers, which indicates its potential involvement in liver fibrosis.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Jinfang Zhao, Lilin Hu, Wenfang Gui, Li Xiao, Weijun Wang, Jing Xia, Huiqian Fan, Zhonglin Li, Qingjing Zhu, Xiaohua Hou, Huikuan Chu, Ekihiro Seki, Ling Yang
Summary: TGF-beta signaling in hepatocytes promotes steatosis and body weight gain, and its specific role in NAFLD is not fully understood. The study found that hepatocyte TGF-beta signaling can promote obesity and fatty liver induced by a high-fat diet by regulating mitochondrial oxidative phosphorylation and suppressing white-to-beige fat conversion. It was also found that let-7b-5p derived from hepatocyte-secreted exosomes plays an important role in this process.
HEPATOLOGY COMMUNICATIONS
(2022)