Loss of the DNA repair protein, polynucleotide kinase/phosphatase, activates the type 1 interferon response independent of ionizing radiation DOI Creative Commons
Wisdom Deebeke Kate,

Mesfin Fanta,

Michael Weinfeld

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(16), P. 9630 - 9653

Published: Aug. 1, 2024

Abstract DNA damage has been implicated in the stimulation of type 1 interferon (T1IFN) response. Here, we show that downregulation repair protein, polynucleotide kinase/phosphatase (PNKP), a variety cell lines causes robust phosphorylation STAT1, upregulation interferon-stimulated genes and persistent accumulation cytosolic DNA, all which are indicators for activation T1IFN Furthermore, this did not require induction by ionizing radiation. Instead, our data revealed production reactive oxygen species (ROS) synergises with PNKP loss to potentiate response, significantly compromises mitochondrial (mtDNA) integrity. Depletion mtDNA or treatment PNKP-depleted cells ROS scavengers abrogated implicating as significant source required The STING signalling pathway is responsible observed increase pro-inflammatory gene signature cells. While response was dependent on ZBP1, cGAS only contributed some lines. Our have implications cancer therapy, since inhibitors would potential stimulate immune also neurological disorders associated mutation.

Language: Английский

Harmful Free Radicals in Aging: A Narrative Review of Their Detrimental Effects on Health DOI
Yasser Fakri Mustafa

Indian Journal of Clinical Biochemistry, Journal Year: 2023, Volume and Issue: 39(2), P. 154 - 167

Published: Aug. 1, 2023

Language: Английский

Citations

56
How the Innate Immune DNA Sensing cGAS-STING Pathway Is Involved in Apoptosis DOI Open Access
Wanglong Zheng,

Anjing Liu,

Nengwen Xia

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 3029 - 3029

Published: Feb. 3, 2023

The cGAS-STING signaling axis can be activated by cytosolic DNA, including both non-self DNA and self DNA. This is used the innate immune system to monitor invading pathogens and/or damage. Increasing evidence has suggested that pathway not only facilitates inflammatory responses production of type I interferons (IFN), but also activates other cellular processes, such as apoptosis. Recently, many studies have focused on analyzing mechanisms apoptosis induced their consequences. review gives a detailed account interplay between induce through ER stress, NLRP3, NF-κB, IRF3, IFN signals. Conversely, feed back regulate pathway, suppressing it via activation caspases or promoting mitochondrial (mtDNA) release. Apoptosis mediated plays crucial roles in balancing responses, resisting infections, limiting tumor growth.

Language: Английский

Citations

47
Hydrogel Loaded with Peptide-Containing Nanocomplexes: Symphonic Cooperation of Photothermal Antimicrobial Nanoparticles and Prohealing Peptides for the Treatment of Infected Wounds DOI
Qiuye Jia, Zhe Fu, Yuansheng Li

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(11), P. 13422 - 13438

Published: March 5, 2024

Current treatment for chronic infectious wounds is limited due to severe drug resistance in certain bacteria. Therefore, the development of new composite hydrogels with nonantibiotic antibacterial and pro-wound repair important. Here, we present a photothermal hydrogel fabricated coating Fe2+ cross-linked carboxymethyl chitosan (FeCMCS) following incorporation melanin nanoparticles (MNPs) CyRL-QN15 peptide. Various physical properties were characterized. Cell proliferation, migration, cycle, free-radical scavenging activity assessed, antimicrobial probed by therapy. The effects validated model methicillin-resistant Staphylococcus aureus (MRSA) infection full-thickness injury. This effect was further confirmed changes cytokines associated inflammation, re-epithelialization, angiogenesis on seventh day after wound formation. MNPs demonstrated robust conversion capabilities. (MNPs/CyRL-QN15/FeCMCS) promoted keratinocyte fibroblast proliferation migration while exhibiting high efficacy, effectively killing more than 95% Gram-positive Gram-negative In vivo study using an MRSA-infected injury good therapeutic efficacy promoting regeneration remodeling chronically infected alleviating inflammatory response accelerating re-epithelialization collagen deposition. MNPs/CyRL-QN15/FeCMCS showed excellent prohealing wounds, indicating potential as promising candidate healing promotion.

Language: Английский

Citations

35
Roles of reactive oxygen species in inflammation and cancer DOI Creative Commons

Yunfei Yu,

Shengzhuo Liu,

Luchen Yang

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(4)

Published: April 1, 2024

Abstract Reactive oxygen species (ROS) constitute a spectrum of oxygenic metabolites crucial in modulating pathological organism functions. Disruptions ROS equilibrium span various diseases, and current insights suggest dual role for tumorigenesis the immune response within cancer. This review rigorously examines production its normal cells, elucidating subsequent regulatory network inflammation Comprehensive synthesis details documented impacts on diverse cells. Exploring intricate relationship between cancer immunity, we highlight influence existing immunotherapies, including checkpoint blockade, chimeric antigen receptors, vaccines. Additionally, underscore promising prospects utilizing targeting modulators as novel immunotherapeutic interventions discusses complex interplay ROS, inflammation, tumorigenesis, emphasizing multifaceted functions both physiological conditions. It also underscores potential implications immunotherapy suggests future research directions, development targeted therapies precision oncology approaches. In summary, this emphasizes significance understanding ROS‐mediated mechanisms advancing therapy developing personalized treatments.

Language: Английский

Citations

35
cGAS-STING pathway as a potential trigger of immunosenescence and inflammaging DOI Creative Commons
Carine Raquel Richter Schmitz, Rafael Moura Maurmann, Fátima Theresinha Costa Rodrigues Guma

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 28, 2023

Aging is associated with an increased incidence of autoimmune diseases, despite the progressive decline immune responses (immunosenescence). This apparent paradox can be explained by age-related chronic low-grade systemic inflammation (inflammaging) and dysregulation innate signaling. During cellular aging, there accumulation damaged DNA in cell's cytoplasm, which serves as ubiquitous danger-associated molecule, promptly recognized sensors. For instance, free cytoplasmic recognized, DNA-sensing molecules like cGAS-STING (cyclic GMP-AMP synthase linked to a stimulator interferon genes), triggering transcriptional factors involved secretion pro-inflammatory mediators. However, contribution this pathway aging system remains largely unknown. Here, we highlight recent advances understanding biology pathway, its influence on senescence-associated secretory phenotype (SASP), modulation during sterile inflammation. We propose that important stress sensor damage also trigger immunosenescence inflammaging.

Language: Английский

Citations

36
Macrophages and tumor-associated macrophages in the senescent microenvironment: From immunosuppressive TME to targeted tumor therapy DOI Creative Commons

Ming Du,

Lu Sun,

J.J. Guo

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 204, P. 107198 - 107198

Published: April 30, 2024

In-depth studies of the tumor microenvironment (TME) have helped to elucidate its cancer-promoting mechanisms and inherent characteristics. Cellular senescence, which acts as a response injury can release senescence-associated secretory phenotypes (SASPs). These SASPs various cytokines, chemokines, growth factors, remodeling TME. This continual development senescent environment could be associated with chronic inflammation immunosuppressive Additionally, influence phenotype function macrophages, leading recruitment tumor-associated macrophages (TAMs). contributes proliferation metastasis in microenvironment, working tandem immune regulation, angiogenesis, therapeutic resistance. comprehensive review covers evolving nature TAMs development. We also explored links between inflammation, TME, cellular macrophages. Moreover, we compiled tumor-specific treatment strategies centered on senescence current challenges research. study aimed clarify mechanism progression advance targeted therapies.

Language: Английский

Citations

12
Mitochondrial Dynamics and Metabolism in Macrophages for Cardiovascular Disease: a review DOI

Yi-lang Zhong,

Chenqin Xu,

Ji Li

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: 140, P. 156620 - 156620

Published: March 7, 2025

Language: Английский

Citations

1
The macrophage STING-YAP axis controls hepatic steatosis by promoting the autophagic degradation of lipid droplets DOI
Tao Yang, Xiaoye Qu, Xiao Wang

et al.

Hepatology, Journal Year: 2023, Volume and Issue: 80(5), P. 1169 - 1183

Published: Oct. 23, 2023

Background and Aims: The hallmark of NAFLD or hepatic steatosis is characterized by lipid droplet (LD) accumulation in hepatocytes. Autophagy may have profound effects on metabolism innate immune response. However, how activation regulate the autophagic degradation intracellular LDs remains elusive. Approach Results: A mouse model a high-fat diet–induced NASH was used myeloid-specific stimulator interferon genes (STING) knockout STING/yes-associated protein (YAP) double mice. Liver injury, accumulation, proteins, genes, chromatin immunoprecipitation coupled with massively parallel sequencing, RNA-Seq were assessed vivo vitro . We found that oxidative stress activates STING YAP pathways macrophages. acrophage deficiency (myeloid-specific knockout) enhances nuclear activity, reduces increases autophagy-related proteins ATG5, ATG7, light chain 3B but diminishes LD perilipin 2 expression. disruption (myeloid serum alanine aminotransferase triglyceride levels β-fatty acid oxidation gene expression augments levels, exacerbating deposition. Chromatin sequencing reveals macrophage targets transmembrane 205 AMP-activated kinase α, which interacts hepatocyte mitofusin induces disulfide isomerase activation. Protein hypoxia-inducible factor-1α signaling, autophagosome colocalization LDs, promotes interacting chaperone-mediated autophagy chaperone HSC70. Conclusions: STING-YAP axis controls reprogramming 205/mitofusin 2/protein isomerase-dependent pathway. These findings highlight regulatory mechanism STING-driven activity control.

Language: Английский

Citations

22
Mitochondria during T cell aging DOI Creative Commons
Jose Ignacio Escrig, Sandra Delgado-Pulido, Marı́a Mittelbrunn

et al.

Seminars in Immunology, Journal Year: 2023, Volume and Issue: 69, P. 101808 - 101808

Published: July 18, 2023

Mitochondrial dysfunction is a hallmark of aging that contributes to inflammaging. It characterized by alterations the mitochondrial DNA, reduced respiratory capacity, decreased membrane potential and increased reactive oxygen species production. These primary disrupt other interconnected important mitochondrial-related processes such as metabolism, dynamics biogenesis, mitophagy, calcium homeostasis or apoptosis. In this review, we gather current knowledge about different which are altered during aging, with special focus on their contribution age-associated T cell

Language: Английский

Citations

19
Understanding the neuronal synapse and challenges associated with the mitochondrial dysfunction in mild cognitive impairment and Alzheimer’s disease DOI
Harkomal Verma, Prabhakar Gangwar,

Anuradha Yadav

et al.

Mitochondrion, Journal Year: 2023, Volume and Issue: 73, P. 19 - 29

Published: Sept. 12, 2023

Language: Английский

Citations

19