Tumor vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA): Suppresses macrophage capping protein beyond STING activation
In this study, we demonstrated that DMXAA binds to both human and mouse macrophage capping protein (CapG), with a KD of 5.839 μM for hCapG and a KD of 2.867 μM for mCapG, as determined by surface plasmon resonance (SPR) analysis. Homology modeling and molecular docking analysis of hCapG indicated that the critical residues involved in the hydrogen bond interaction of DMXAA with hCapG were Arg153, Thr151, and GLN141, Asn234. In addition, electrostatic pi-cation interaction occurred between DMXAA and hCapG. Further functional studies revealed that CapG protein plays a crucial role in the effects of DMXAA on human umbilical...
Source: Biochimica et Biophysica Acta - April 2, 2024 Category: Biochemistry Authors: Zhiyong Xiao Xia Cui Feng Liu Ying Wang Xiao Liu Wenxia Zhou Yongxiang Zhang Source Type: research
IGF2 promotes alveolar bone regeneration in murine periodontitis via inhibiting cGAS/STING-mediated M1 macrophage polarization
This study evaluated the role of insulin-like growth factor 2 (IGF2) in periodontitis by inhibiting the polarization of M1 macrophages via the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway. IGF2 was enriched in the gingival tissue of murine periodontitis model identified by RNA sequencing. IGF2 application alleviated the expression of pro-inflammatory factors and promoted osteogenesis and the expression of related genes and proteins in a dose-dependent manner in periodontitis. The result of micro-CT verified this finding. Both in vivo and in vitro results revealed that IGF2 decreased the pol...
Source: International Immunopharmacology - April 2, 2024 Category: Allergy & Immunology Authors: Tairan Wang Yi Tang Yuxing Xia Qian Zhang Shaokang Cao Miaomiao Bie Feiwu Kang Source Type: research
Salvianolic acid A prevents UV-induced skin damage by inhibiting the cGAS-STING pathway
Int Immunopharmacol. 2024 Apr 1;132:111971. doi: 10.1016/j.intimp.2024.111971. Online ahead of print.ABSTRACTDNA damage resulting from UV irradiation on the skin has been extensively documented in numerous studies. In our prior investigations, we demonstrated that UVB-induced DNA breakage from keratinocytes can activate the cGAS-STING pathway in macrophages. The cGAS-STING signaling pathway serves as the principal effector for detecting and responding to abnormal double-stranded DNA in the cytoplasm. Expanding on our previous findings, we have further validated that STING knockout significantly diminishes UVB-induced skin ...
Source: International Immunopharmacology - April 2, 2024 Category: Allergy & Immunology Authors: Zhenqi Zuo Shengwei He Yinqi Qiu Runying Guo Yingxue He Chenyang Jiao Yugui Xia Wen Liu Chao Luan Wenjie Guo Source Type: research
DNA Damage-driven Inflammatory Cytokines: Reprogramming of Tumor Immune Microenvironment and Application of Oncotherapy
AbstractDNA damage occurs across tumorigenesis and tumor development. Tumor intrinsic DNA damage can not only increase the risk of mutations responsible for tumor generation but also initiate a cellular stress response to orchestrate the tumor immune microenvironment (TIME) and dominate tumor progression. Accumulating evidence documents that multiple signaling pathways, including cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) and ataxia telangiectasia-mutated protein/ataxia telangiectasia and Rad3-related protein (ATM/ATR), are activated downstream of DNA damage and they are associated with the secreti...
Source: Journal of Huazhong University of Science and Technology -- Medical Sciences -- - April 2, 2024 Category: Research Source Type: research
Activation of STING by the novel liposomal TLC388 enhances the therapeutic response to anti-PD-1 antibodies in combination with radiotherapy
AbstractCurrent immune checkpoint inhibiters (ICIs) have contrasting clinical results in poorly immunogenic cancers such as microsatellite-stable colorectal cancer (MSS-CRC). Therefore, understanding and developing the combinational therapeutics for ICI-unresponsive cancers is critical. Here, we demonstrated that the novel topoisomerase I inhibitor TLC388 can reshape the tumor immune landscape, corroborating their antitumor effects combined with radiotherapy as well as immunotherapy. We found that TLC388 significantly triggered cytosolic single-stranded DNA (ssDNA) accumulation for STING activation, leading to type I inter...
Source: Cancer Immunology, Immunotherapy - April 2, 2024 Category: Cancer & Oncology Source Type: research
Use of point-of-care ultrasound to assess the severity of scorpion stings in hospitalized patients
. (Source: Clinical Toxicology)
Source: Clinical Toxicology - April 2, 2024 Category: Toxicology Authors: Juliana Sartorelo AlmeidaCecilia Gomez RavettiMarcus Vin ícius de Melo AndradeAdebal de Andrade FilhoRafael Silva e CastroPedro Pires Costa PimentaPaula Frizera VassalloVandack Nobrea Departamento de Toxicologia do Hospital João XXIII, Centro de Informa Source Type: research
Necroptosis Induced by Prolonged Cold Static Preservation of Lungs Depends on the cGAS-Sting Pathway
Purpose: Prolonged cold static lung preservation is known to induce a programmed cell death termed necroptosis. The present study describes a new mechanism by which prolonged exposition to a 4 °C temperature promotes necroptosis by activating the cGAS-STING cytosolic DNA sensor system both in a cellular model and in rat lungs. (Source: The Journal of Heart and Lung Transplantation)
Source: The Journal of Heart and Lung Transplantation - April 1, 2024 Category: Transplant Surgery Authors: , A. Debonneville, R. Parapanov, M. Allouche, L. Liaudet, T. Krueger Source Type: research
mt-DNA Aggravation Primary Graft Dysfunction Inflammatory Response Through GSDMD Dependent cGAS-STING-NLRP3 Feedback Loop
Purpose: Lung ischemia-reperfusion injury is thought to initiate primary graft dysfunction (PGD) by stimulating inflammation. The elevation of mt-DNA is associated with severe PGD, which can activate GSDMD and trigger mitochondrial damage in pulmonary vascular endothelial cells, further promoting the elevation of mtDNA, and which is closely related to alveolar macrophages (AM) activation. However, the feedback loop triggered by mt-DNA through GSDMD and the interaction between pulmonary vascular endothelial cells and AM in PGD are still unknown. (Source: The Journal of Heart and Lung Transplantation)
Source: The Journal of Heart and Lung Transplantation - April 1, 2024 Category: Transplant Surgery Authors: , J. Chen, M. Huang, J. Zhao Source Type: research
The cGAS-Sting Pathway Drives Alveolar Epithelial Cell Death via Non-Canonical PKR Signaling During Lung Ischemia-Reperfusion Injury
Purpose: The cGAS-STING pathway, a critical component of cytosolic DNA sensing, plays a pivotal role in regulating inflammation-related diseases. Our study aims to investigate the involvement of the cGAS-STING pathway and its regulatory mechanism in lung ischemia-reperfusion injury (LIRI), providing novel insights into potential therapeutic targets for primary graft dysfunction (PGD). (Source: The Journal of Heart and Lung Transplantation)
Source: The Journal of Heart and Lung Transplantation - April 1, 2024 Category: Transplant Surgery Authors: , C. Li, H. Liu, C. Chen, J. Wu Source Type: research
Cholesterol-binding motifs in STING that control endoplasmic reticulum retention mediate anti-tumoral activity of cholesterol-lowering compounds
Nat Commun. 2024 Mar 29;15(1):2760. doi: 10.1038/s41467-024-47046-5.ABSTRACTThe cGAS-STING pathway plays a crucial role in anti-tumoral responses by activating inflammation and reprogramming the tumour microenvironment. Upon activation, STING traffics from the endoplasmic reticulum (ER) to Golgi, allowing signalling complex assembly and induction of interferon and inflammatory cytokines. Here we report that cGAMP stimulation leads to a transient decline in ER cholesterol levels, mediated by Sterol O-Acyltransferase 1-dependent cholesterol esterification. This facilitates ER membrane curvature and STING trafficking to Golgi...
Source: Cancer Control - March 30, 2024 Category: Cancer & Oncology Authors: Bao-Cun Zhang Marlene F Laursen Lili Hu Hossein Hazrati Ryo Narita Lea S Jensen Aida S Hansen Jinrong Huang Yan Zhang Xiangning Ding Maimaitili Muyesier Emil Nilsson Agnieszka Banasik Christina Zeiler Trine H Mogensen Anders Etzerodt Ralf Agger Mogens Joh Source Type: research
GSE247045 Mitochondrial injury induced by a Salmonella genotoxin triggers the proinflammatory senescence-associated secretory phenotype
Contributors : Han-Yi Chen ; Huei-Ying Li ; Po-Yo Liu ; Shu-Jung ChangSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensBacterial genotoxins can damage host cells by targeting their chromosomal DNA. Salmonella Typhi the causative pathogen of typhoid fever in humans, secretes an essential genotoxin called typhoid toxin, which can induce cellular senescence. Here we show that typhoid toxin triggers the senescence-associated secretory phenotype (SASP) by disrupting mitochondrial function, including a decrease in mitochondrial DNA (mtDNA) content and a disturbance of redox homeostasis w...
Source: GEO: Gene Expression Omnibus - March 30, 2024 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Exposure to polystyrene nanoplastics induces abnormal activation of innate immunity via the cGAS-STING pathway
Ecotoxicol Environ Saf. 2024 Mar 28;275:116255. doi: 10.1016/j.ecoenv.2024.116255. Online ahead of print.ABSTRACTEndogenous immune defenses provide an intrinsic barrier against external entity invasion. Microplastics in the environment, especially those at the nanoscale (nanoplastics or NPs), may pose latent health risks through direct exposure. While links between nanoplastics and inflammatory processes have been established, detailed insights into how they may perturb the innate immune mechanisms remain uncharted. Employing murine and macrophage (RAW264.7) cellular models subjected to polystyrene nanoplastics (PS-NPs), o...
Source: Ecotoxicology and Environmental Safety - March 29, 2024 Category: Environmental Health Authors: Xiaochang Liu Lihui Xuan Yin Wang Can Qu Wensen Yi Jingjing Yang Huiji Pan Jing Zhang Cuimei Chen Chenjun Bai Ping-Kun Zhou Ruixue Huang Source Type: research
Vaccination with a combination of STING agonist-loaded lipid nanoparticles and CpG-ODNs protects against lung metastasis via the induction of CD11bhighCD27low memory-like NK cells
ConclusionAs far as could be ascertained, this is the first report of the in vivo induction, identification, and confirmation of a phenotype of the memory-like NK cells through a prophylactic effect via the use of an immunotherapeutic drug. Our findings provide novel insights into the in vivo induction of CD11bhighCD27low memory-like NK cells thus paving the way for the development of efficient immunotherapies.Graphical Abstract (Source: Experimental Hematology and Oncology)
Source: Experimental Hematology and Oncology - March 29, 2024 Category: Cancer & Oncology Source Type: research
Discovery of a triphenylamine-based ligand that targets mitochondrial DNA G-quadruplexes and activates the cGAS-STING immunomodulatory pathway
In this study, we engineered a series of triphenylamine-based analogues targeting mtDNA G4s, and A6 was determined as the most promising compound. Cellular studies indicated that A6 caused severe mtDNA damage. Then, damaged mtDNA stimulated cGAS-STING pathway, resulting in the following cytokine production of tumor cells and the maturation of DCs. In vivo experiments certified that A6 exerted suppressive influences on tumor growth and metastasis in 4T1 cell-bearing mice by the regulation of TME, including the remodeling of macrophages and the activation of T cells. To our knowledge, it is the first time to report a ligand ...
Source: European Journal of Medicinal Chemistry - March 28, 2024 Category: Chemistry Authors: Xiao-Dong Wang Yong-Si Liu Meng-Die Chen Ming-Hao Hu Source Type: research
