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JOURNAL ARTICLE
Manon Defaye, Amyaouch Bradaia, Nasser S Abdullah, Francina Agosti, Mircea Iftinca, Mélissa Delanne-Cuménal, Vanessa Soubeyre, Kristofer Svendsen, Gurveer Gill, Aye Ozmaeian, Nadine Gheziel, Jérémy Martin, Gaetan Poulen, Nicolas Lonjon, Florence Vachiery-Lahaye, Luc Bauchet, Lilian Basso, Emmanuel Bourinet, Isaac M Chiu, Christophe Altier
Inflammation and pain are intertwined responses to injury, infection, or chronic diseases. While acute inflammation is essential in determining pain resolution and opioid analgesia, maladaptive processes occurring during resolution can lead to the transition to chronic pain. Here we found that inflammation activates the cytosolic DNA-sensing protein stimulator of IFN genes (STING) in dorsal root ganglion nociceptors. Neuronal activation of STING promotes signaling through TANK-binding kinase 1 (TBK1) and triggers an IFN-β response that mediates pain resolution...
March 19, 2024: Journal of Clinical Investigation
#2
JOURNAL ARTICLE
Hua-Fang Bao, Chun-Hui She, Cheng-Cheng Hou, Da-Nian Ji, Dan Hu, Jun Zou, Yan Shen, Lei-Lei Jian, Jian-Fei Cai, Jing-Fen Ye, Dan Luo, Hai-Fen Ma, Jian-Long Guan
Inflammatory signals from immunological cells may cause damage to intestinal epithelial cells (IECs), resulting in intestinal inflammation and tissue impairment. Interferon-γ-inducible protein 16 (IFI16) was reported to be involved in the pathogenesis of Behçet's syndrome (BS). This study aimed to investigate how inflammatory cytokines released by immunological cells and IFI16 participate in the pathogenesis of intestinal BS. RNA sequencing and real-time quantitative PCR (qPCR) showed that the positive regulation of tumor necrosis factor-α (TNF-α) production in peripheral blood mononuclear cells (PBMCs) of intestinal BS patients may be related to the upregulation of polo like kinase 1 (PLK1) in PBMCs (P = 0...
April 27, 2024: FEBS Journal
#3
JOURNAL ARTICLE
Liang Liu, Mitsuyo Matsumoto, Miki Watanabe-Matsui, Tadashi Nakagawa, Yuko Nagasawa, Jingyao Pang, Bert K K Callens, Akihiko Muto, Kyoko Ochiai, Hirotaka Takekawa, Mahabub Alam, Hironari Nishizawa, Mikako Shirouzu, Hiroki Shima, Keiko Nakayama, Kazuhiko Igarashi
BTB and CNC homology 1 (BACH1) represses the expression of genes involved in the metabolism of iron, heme and reactive oxygen species. While BACH1 is rapidly degraded when it is bound to heme, it remains unclear how BACH1 degradation is regulated under other conditions. We found that FBXO22, a ubiquitin ligase previously reported to promote BACH1 degradation, polyubiquitinated BACH1 only in the presence of heme in a highly purified reconstitution assay. In parallel to this regulatory mechanism, TANK binding kinase 1 (TBK1), a protein kinase that activates innate immune response and regulates iron metabolism via ferritinophagy, was found to promote BACH1 degradation when overexpressed in 293T cells...
April 9, 2024: International Journal of Molecular Sciences
#4
JOURNAL ARTICLE
Ju Hye Jang, Hyun Kim, Ha Rang Kim, Ju Hyun Cho
Deubiquitinating enzyme A (DUBA), a member of the ovarian tumor (OTU) subfamily of deubiquitinases (DUBs), is recognized for its negative regulatory role in type I interferon (IFN) expression downstream of Toll-like receptor 3 (TLR3). However, its involvement in the TLR3 signaling pathway in fish remains largely unexplored. In this study, we investigated the regulatory role of DUBA (OmDUBA) in the TLR3 response in rainbow trout (Oncorhynchus mykiss). OmDUBA features a conserved OTU domain, and its expression increased in RTH-149 cells following stimulation with the TLR3 agonist poly(I:C)...
April 24, 2024: Fish & Shellfish Immunology
#5
JOURNAL ARTICLE
Yue Wang, Wen Niu, Shan Zhu, Jianyu Sun, Jianrui Lv, Ning Wang, Huijuan Zhang, Zhenni Zhang, Meijuan Wang, Lingli Cao, Shuwei Li, Qian Zhai, Lei Ma
Sleep deprivation (SD) has been associated with several adverse effects, including cognitive deficit. Emerging evidence suggests microglia-associated neuroinflammation is a potential trigger of cognitive deficit after SD. Stimulator of interferon genes (STING) constitutes an important factor in host immune response to pathogenic organisms and is found in multiple cells, including microglia. STING is involved in neuroinflammation during neuronal degeneration, although how STING signaling affects SD-induced neuroinflammation remains unexplored...
April 26, 2024: Inflammation
#6
JOURNAL ARTICLE
Haiping Zhang, Lijun Jiang, Xinyi Du, Zhen Qian, Guizhu Wu, Ying Jiang, Zhiyong Mao
As the major DNA sensor that activates the STING-TBK1 signaling cascade, cGAS is mainly present in the cytosol. A number of recent reports have indicated that cGAS also plays critical roles in the nucleus. Our previous work demonstrated for the first time that cGAS is translocated to the nucleus upon the occurrence of DNA damage and inhibits homologous recombination (HR), one of the two major pathways of DNA double strand break (DSB) repair. However, whether nuclear cGAS regulates the other DSB repair pathway, nonhomologous end joining (NHEJ), which can be further divided into the less error-prone canonical NHEJ (c-NHEJ) and more mutagenic alternative NHEJ (alt-NHEJ) subpathways, has not been characterized...
April 25, 2024: Cell Death and Differentiation
#7
JOURNAL ARTICLE
Bei Wu, Dianyu Li, Huisheng Bai, Rongqian Mo, Hongshan Li, Jingying Xie, Xiangbo Zhang, Yanmei Yang, Huixia Li, Adi Idris, Xiangrong Li, Ruofei Feng
Mammalian reovirus (MRV) is a non-enveloped, gene segmented double-stranded RNA (dsRNA) virus. It is an important zoonotic pathogen that infects many mammals and vertebrates that act as natural hosts and causes respiratory and digestive tract diseases. Studies have reported that RIG-I and MDA5 in the innate immune cytoplasmic RNA-sensing RIG-like receptor (RLR) signaling pathway can recognize dsRNA from MRV and promote antiviral type I interferon (IFN) responses. However, the mechanism by which many MRV-encoded proteins evade the host innate immune response remains unclear...
April 24, 2024: Molecular Immunology
#8
JOURNAL ARTICLE
Jian Yin, Peng Lai, Libo Zhu, Jinzhong Ma
Osteolysis resulting from wear particles and subsequent aseptic loosening is a leading cause of revision surgery of artificial joints. The underlying pathogenesis of particle-induced osteolysis (PPO) has remained largely uncertain. Addressing how to mitigate osteolysis caused by wear particles presents a significant challenge for orthopedic surgeons. This study aimed to explore the molecular mechanism by which Angiopoietin (Ang-1) inhibits osteoclast activation to alleviate osteolysis. RAW264.7 mouse macrophages were stimulated with LPS or RANKL to induce osteoclast formation...
April 25, 2024: Applied Biochemistry and Biotechnology
#9
JOURNAL ARTICLE
Chao Wei, Qing Huang, Fanxing Zeng, Li Ma, Xiaofei Bai, Xuejing Zhu, Hua Gao, Xiaolin Qi
The activation of innate immunity following transplantation has been identified as a crucial factor in allograft inflammation and rejection. However, the role of cGAS/STING signaling-mediated innate immunity in the pathogenesis of allograft rejection remains unclear. Utilizing a well-established murine model of corneal transplantation, we demonstrated increased expression of cGAS and STING in rejected corneal allografts compared to syngeneic and normal corneas, along with significant activation of the cGAS/STING pathway, as evidenced by the enhanced phosphorylation of TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3)...
April 20, 2024: American Journal of Transplantation
#10
JOURNAL ARTICLE
Xiying Tan, Qianqian Chen, Zhonghua Chen, Zhenzhen Sun, Wei Chen, Ruifen Wei
PURPOSE: The cGAS-STING pathway has been shown to be an important mediator of inflammation. There is emerging evidence of the importance of this signaling cascade in a variety of inflammatory diseases settings. Here, we present evidence that the mitochondrial DNA (mtDNA) damage-mediated cGAS-STING pathway plays an important role in the induction of inflammation in environmental dry eye (DE). METHODS: RT-qPCR and Western blot were used to assess the induction of the cGAS-STING pathway and inflammatory cytokines in environmental DE mouse model, primary human corneal epithelial cells (pHCECs), and patients with DE...
April 1, 2024: Investigative Ophthalmology & Visual Science
#11
JOURNAL ARTICLE
Yang Li, Boqing Dong, Ying Wang, Huanjing Bi, Jing Zhang, Chenguang Ding, Chenge Wang, Xiaoming Ding, Wujun Xue
Mitochondrial dysfunction is recognized as a pivotal contributor to the pathogenesis of renal ischemia-reperfusion (IR) injury. Mitophagy, the process responsible for removing damaged protein aggregates, stands as a critical mechanism safeguarding cells against IR injury. Currently, the role of deubiquitination in regulating mitophagy still needs to be completely elucidated. This study aimed to evaluate the impact of ubiquitin-specific peptidase 14 (Usp14), a deubiquitinase, in IR injury by influencing mitophagy...
April 19, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
#12
JOURNAL ARTICLE
Shiyun Chen, Jingjing Li, Luda Yan, Xianhao Zhang, Jiesi Huang, Peng Zhou
PURPOSE: To investigate the therapeutic effect of electroacupuncture (EA) on chronic and unpredictable mild stress (CUMS)-induced depression in mice and the underlying mechanism. METHODS: Male C57BL/6 mice were randomly divided into 6 groups: Control, CUMS, CUMS+EA-placebo, CUMS+EA, CUMS+ ad-NC, CUMS+ ad-cGAS-shRNA. CUMS was utilized to establish the depression model in mice. The behavioral changes were determined by the forced swimming, open field, and sucrose preference experiments...
April 19, 2024: Aging
#13
JOURNAL ARTICLE
Yanwei Zhang, Jing Cen, Haixia Wu, Wa Gao, Zhiying Jia, Mikolaj Adamek, Jun Zou
HnRNP A/B belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) family and plays an important role in regulating viral protein translation and genome replication. Here, we found that overexpression of hnRNP A/B promoted Spring viremia of carp virus (SVCV) and Cyprinid herpesvirus 3 (CyHV3) replication. Further, hnRNP A/B was shown to act as a negative regulator of type I interferon (IFN) response. Mechanistically, hnRNP A/B interacted with MITA, TBK1 and IRF3 to initiate their degradation. In addition, hnRNP A/B bound to the kinase domain of TBK1, the C terminal domain of MITA and IAD domain of IRF3, and the RRM1 domain of hnRNP A/B bound to TBK1, RRM2 domain bound to IRF3 and MITA...
April 18, 2024: Fish & Shellfish Immunology
#14
JOURNAL ARTICLE
Yajie Hu, Minigmei Zhong, Yaming Lv, Wei Zhao, Baojiang Qian, Jie Song, Yunhui Zhang
Coxsackievirus-A10 (CV-A10), responsible for the hand, foot and mouth disease (HFMD) pandemic, could cause serious central nervous system (CNS) complications. The underlying molecular basis of CV-A10 and host interactions inducing neuropathogenesis is still unclear. The Hippo signaling pathway, historically known for a dominator of organ development and homeostasis, has recently been implicated as an immune regulator. However, its role in host defense against CV-A10 has not been investigated. Herein, it was found that CV-A10 proliferated in HMC3 cells and promoted the release of inflammatory cytokines...
April 19, 2024: Virology Journal
#15
JOURNAL ARTICLE
Haidong Ding, Rina Wu
BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by airflow limitation and inflammation resulting from genetic and environmental factors, notably cigarette smoke. Pyroptosis, a cell death process, is implicated in COPD, but its mechanisms are unclear. SHP2, a phosphatase, modulates inflammatory pathways, suggesting a role in COPD pathogenesis and potential therapeutic avenues. OBJECTIVE: This study investigates the mechanism by which SHP2 regulates cell pyroptosis in bronchial epithelial cells in COPD patients...
April 18, 2024: Alternative Therapies in Health and Medicine
#16
JOURNAL ARTICLE
Shanhui Liu, Kanak Joshi, Lei Zhang, Wenyan Li, Ryan Mack, Austin Runde, Patrick A Hagen, Kevin Barton, Peter Breslin, Hong-Long Ji, Ameet R Kini, Zhiping Wang, Jiwang Zhang
Myelodysplastic syndromes (MDS) are a heterogeneous group of pre-leukemic hematopoietic disorders characterized by cytopenia in peripheral blood due to ineffective hematopoiesis and normo- or hypercellularity and morphologic dysplasia in bone marrow (BM). An inflammatory BM microenvironment and programmed cell death of hematopoietic stem/progenitor cells (HSPCs) are thought to be the major causes of ineffective hematopoiesis in MDS. Pyroptosis, apoptosis and necroptosis (collectively, PANoptosis) are observed in BM tissues of MDS patients, suggesting an important role of PANoptosis in MDS pathogenesis...
April 18, 2024: Cell Death & Disease
#17
JOURNAL ARTICLE
Jin-Feng Tong, Lang Yu, Rui-Hai Gan, Li-Ping Shi, Shao-Yang Bu, Yue Gu, Xin Wen, Jun-Long Sun, Fei-Biao Song, Li Zhou, Jian-Fang Gui, Jian Luo
Pompano fishes have been widely farmed worldwide. As a representative commercial marine species of the Carangidae family, the golden pompano (Trachinotus blochii) has gained significant popularity in China and worldwide. However, because of rapid growth and high-density aquaculture, the golden pompano has become seriously threatened by various diseases. Cell lines are the most cost-effective resource for in vitro studies and are widely used for physiological and pathological research owing to their accessibility and convenience...
April 16, 2024: Fish & Shellfish Immunology
#18
JOURNAL ARTICLE
Can Yang, Juanjuan Shu, Xiao Yang, Yujia Miao, Ji Liu, Jun Li, Jun Xiao, Weiguang Kong, Zhen Xu, Hao Feng
USP14 regulates the immune related pathways by deubiquitinating the signaling molecules in mammals. In teleost, USP14 is also reported to inhibit the antiviral immune response through TBK1, but its regulatory mechanism remains obscure. To elucidate the role of USP14 in the RLR/IFN antiviral pathway in teleost, the homolog USP14 (bcUSP14) of black carp (Mylopharyngodon piceus) has been cloned and characterize in this paper. bcUSP14 contains 490 amino acids (aa), and the sequence is well conserved among in vertebrates...
April 16, 2024: Fish & Shellfish Immunology
#19
JOURNAL ARTICLE
Xiu-Qing Li, Meng-Pan Cai, Ming-Yang Wang, Bo-Wen Shi, Guo-Yu Yang, Jiang Wang, Bei-Bei Chu, Sheng-Li Ming
The pseudorabies virus (PRV) is identified as a double-helical DNA virus responsible for causing Aujeszky's disease, which results in considerable economic impacts globally. The enzyme tryptophanyl-tRNA synthetase 2 (WARS2), a mitochondrial protein involved in protein synthesis, is recognized for its broad expression and vital role in the translation process. The findings of our study showed an increase in both mRNA and protein levels of WARS2 following PRV infection in both cell cultures and animal models...
April 16, 2024: Virologica Sinica
#20
Marijne Vandebergh, Eliana Marisa Ramos, Nick Corriveau-Lecavalier, Vijay K Ramanan, John Kornak, Carly Mester, Tyler Kolander, Danielle Brushaber, Adam M Staffaroni, Daniel Geschwind, Amy Wolf, Kejal Kantarci, Tania F Gendron, Leonard Petrucelli, Marleen Van den Broeck, Sarah Wynants, Matthew C Baker, Sergi Borrego-Écija, Brian Appleby, Sami Barmada, Andrea Bozoki, David Clark, R Ryan Darby, Bradford C Dickerson, Kimiko Domoto-Reilly, Julie A Fields, Douglas R Galasko, Nupur Ghoshal, Neill Graff-Radford, Ian M Grant, Lawrence S Honig, Ging-Yuek Robin Hsiung, Edward D Huey, David Irwin, David S Knopman, Justin Y Kwan, Gabriel C Léger, Irene Litvan, Joseph C Masdeu, Mario F Mendez, Chiadi Onyike, Belen Pascual, Peter Pressman, Aaron Ritter, Erik D Roberson, Allison Snyder, Anna Campbell Sullivan, M Carmela Tartaglia, Dylan Wint, Hilary W Heuer, Leah K Forsberg, Adam L Boxer, Howard J Rosen, Bradley F Boeve, Rosa Rademakers
BACKGROUND AND OBJECTIVES: TMEM106B has been proposed as a modifier of disease risk in FTLD-TDP, particularly in GRN mutation carriers. Furthermore, TMEM106B has been investigated as a disease modifier in the context of healthy aging and across multiple neurodegenerative diseases. The objective of this study is to evaluate and compare the effect of TMEM106B on gray matter volume and cognition in each of the common genetic FTD groups and in sporadic FTD patients. METHODS: Participants were enrolled through the ARTFL/LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study, which includes symptomatic and presymptomatic individuals with a pathogenic mutation in C9orf72, GRN, MAPT, VCP, TBK1, TARDBP, symptomatic non-mutation carriers, and non-carrier family controls...
April 5, 2024: medRxiv
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