DAMPs and NETs in Sepsis

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: Oct. 30, 2019

Sepsis is a deadly inflammatory syndrome caused by an exaggerated immune response to infection. Much has been focused on host pathogens mediated through the interaction of pathogen-associated molecular patterns (PAMPs) and pattern recognition receptors (PRRs). PRRs are also activated nuclear, mitochondrial, cytosolic proteins, known as damage-associated (DAMPs) that released from cells during sepsis. Some well described members DAMP family extracellular cold-inducible RNA-binding protein (eCIRP), high mobility group box 1 (HMGB1), histones, adenosine triphosphate (ATP). DAMPs cell inflammasome activation or passively following death. Similarly, neutrophil traps (NETs) neutrophils inflammation. NETs webs DNA decorated with myeloperoxidase, elastase. Although contribute pathogen clearance, excessive NET formation promotes inflammation tissue damage in Here, we review their crosstalk sepsis respect sources, activation, release, function. A clear understating DAMPs, crucial for understanding pathophysiology development novel therapeutics.

Language: Английский

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Release mechanisms of major DAMPs

APOPTOSIS, Journal Year: 2021, Volume and Issue: 26(3-4), P. 152 - 162

Published: March 13, 2021

Abstract Damage-associated molecular patterns (DAMPs) are endogenous molecules which foment inflammation and associated with disorders in sepsis cancer. Thus, therapeutically targeting DAMPs has potential to provide novel effective treatments. When establishing anti-DAMP strategies, it is important not only focus on the as inflammatory mediators but also take into account underlying mechanisms of their release from cells tissues. can be released passively by membrane rupture due necrosis/necroptosis, although appear differ between DAMPs. Other types cell death, such apoptosis, pyroptosis, ferroptosis NETosis, contribute DAMP release. In addition, some exported actively live exocytosis secretory lysosomes or exosomes, ectosomes, activation channel pores. Here we review shared DAMP-specific reported literature for high mobility group box 1, ATP, extracellular cold-inducible RNA-binding protein, histones, heat shock proteins, RNAs cell-free DNA.

Language: Английский

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Neutrophil Extracellular Traps and Their Implications in Cardiovascular and Inflammatory Disease

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(2), P. 559 - 559

Published: Jan. 8, 2021

Neutrophils are primary effector cells of innate immunity and fight infection by phagocytosis degranulation. Activated neutrophils also release neutrophil extracellular traps (NETs) in response to a variety stimuli. These NETs net-like complexes composed cell-free DNA, histones granule proteins. Besides the evolutionarily conserved mechanism capture eliminate pathogens, associated with pathophysiological processes various diseases. Here, we elucidate mechanisms NET formation their different implications disease. We focused on autoinflammatory cardiovascular disorders as leading cause death. Neutrophil not only present diseases but play an essential role atherosclerotic plaque formation, arterial venous thrombosis, well development progression abdominal aortic aneurysms. Furthermore, NETosis can be considered source autoantigens maintains inflammatory milieu promoting autoimmune Indeed, there is further need for research into balance between induction, inhibition, degradation order pharmacologically target compounds without impairing patient's immune defense. This review may interest both basic scientists clinicians stimulate translational innovative clinical approaches.

Language: Английский

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Pyroptosis-induced inflammation and tissue damage

Seminars in Immunology, Journal Year: 2023, Volume and Issue: 69, P. 101781 - 101781

Published: June 21, 2023

Language: Английский

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Extracellular CIRP as an endogenous TREM-1 ligand to fuel inflammation in sepsis

JCI Insight, Journal Year: 2020, Volume and Issue: 5(5)

Published: Feb. 6, 2020

Extracellular cold-inducible RNA-binding protein (eCIRP) is a recently discovered damage-associated molecular pattern. Understanding the precise mechanism by which it exacerbates inflammation essential. Here we identified that eCIRP new biologically active endogenous ligand of triggering receptor expressed on myeloid cells-1 (TREM-1), fueling in sepsis. Surface plasmon resonance revealed strong binding affinity between and TREM-1, fluorescence energy transfer assay confirmed eCIRP's interaction with TREM-1 macrophages. Targeting its siRNA or decoy peptide, LP17, using TREM-1–/– mice dramatically reduced eCIRP-induced inflammation. We developed potentially novel 7-aa peptide derived from human eCIRP, M3, blocked eCIRP. M3 suppressed induced agonist antibody cross-linking murine macrophages peripheral blood monocytes. also inhibited systemic tissue injury. Treatment further protected sepsis, improved acute lung injury, increased survival. Thus, have to block eCIRP–TREM-1 improve outcomes

Language: Английский

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The Role of Epithelial Damage in the Pulmonary Immune Response

Cells, Journal Year: 2021, Volume and Issue: 10(10), P. 2763 - 2763

Published: Oct. 15, 2021

Pulmonary epithelial cells are widely considered to be the first line of defence in lung and responsible for coordinating innate immune response injury subsequent repair. Consequently, communicate with multiple cell types including fibroblasts promote acute inflammation normal wound healing damage. However, aberrant death damage hallmarks pulmonary disease, necrotic cellular senescence contributing disease pathogenesis numerous respiratory diseases such as idiopathic fibrosis (IPF), chronic obstructive (COPD) coronavirus (COVID)-19. In this review, we summarise literature that demonstrates plays a pivotal role dysregulation leading tissue destruction abnormal remodelling several diseases. Specifically, highlight epithelial-derived damage-associated molecular patterns (DAMPs) shaping assess their contribution inflammatory fibrotic signalling pathways lung.

Language: Английский

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The interplay of DAMPs, TLR4, and proinflammatory cytokines in pulmonary fibrosis

Journal of Molecular Medicine, Journal Year: 2021, Volume and Issue: 99(10), P. 1373 - 1384

Published: July 13, 2021

Abstract Pulmonary fibrosis is a chronic debilitating condition characterized by progressive deposition of connective tissue, leading to steady restriction lung elasticity, decline in function, and median survival 4.5 years. The causes pulmonary are inhalation foreign particles (such as silicosis pneumoconiosis), infections post COVID-19), autoimmune diseases systemic the tissue), idiopathic fibrosis. therapeutics currently available for only modestly slow progression disease. This review centered on interplay damage-associated molecular pattern (DAMP) molecules, Toll-like receptor 4 (TLR4), inflammatory cytokines TNF-α, IL-1β, IL-17) they contribute pathogenesis fibrosis, possible avenues develop effective that disrupt this interplay.

Language: Английский

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Extracellular CIRP Promotes GPX4-Mediated Ferroptosis in Sepsis

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 29, 2022

Sepsis is characterized by life-threatening organ dysfunction caused a dysregulated host response to infection. Extracellular cold-inducible RNA-binding protein (eCIRP) damage-associated molecular pattern (DAMP) that promotes inflammation and induces cell death via apoptosis, NETosis, and/or pyroptosis. Ferroptosis form of regulated the accumulation lipid peroxide on cellular membranes. We hypothesize eCIRP ferroptosis in macrophages lung tissue during sepsis. RAW 264.7 cells stimulated with recombinant murine (rm) CIRP significantly decreased expression glutathione peroxidase 4 (GPX4), negative regulator ferroptosis, increased reactive oxygen species (ROS) TLR4 dependent manner. In TLR4-/- peritoneal macrophages, depression GPX4 increase ROS levels were attenuated after rmCIRP-treatment compared WT macrophages. rmCIRP also induced which was corrected inhibitor, ferrostatin-1 (Fer-1). Intraperitoneal injection tissue, whereas reduced Fer-1 treatment. decreased, while malondialdehyde (MDA), iron levels, injury scores lungs mice cecal ligation puncture (CLP)-induced sepsis CIRP-/- mice. Treatment C23, specific CLP alleviated decrease MDA tissue. These findings suggest septic decreasing increasing ROS. Therefore, regulation targeting may provide new therapeutic approach other inflammatory diseases.

Language: Английский

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Types of necroinflammation, the effect of cell death modalities on sterile inflammation

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(5)

Published: May 2, 2022

Distinct types of immune responses are activated by infections, which cause the development type I, II, or III inflammation, regulated Th1, Th2, Th17 helper T cells and ILC1, ILC2 ILC3 cells, respectively. While classification to different groups pathogens is widely accepted, subtypes response elicited sterile inflammation have not yet been detailed. Necroinflammation associated with release damage-associated molecular patterns (DAMP) from dying cells. In this review, we present that distinct mechanisms during apoptosis, necroptosis, pyroptosis, ferroptosis lead DAMPs their suppressors, SAMPs. We summarize currently available data on how cell death pathways released SAMPs direct differentiation ILC Understanding necroinflammation can be crucial in developing strategies for treatment inflammatory diseases caused processes.

Language: Английский

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Exosome-derived CIRP: An amplifier of inflammatory diseases

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

Published: Feb. 14, 2023

Cold-inducible RNA-binding protein (CIRP) is an intracellular stress-response and a type of damage-associated molecular pattern (DAMP) that responds to various stress stimulus by altering its expression mRNA stability. Upon exposure ultraviolet (UV) light or low temperature, CIRP get translocated from the nucleus cytoplasm through methylation modification stored in granules (SG). During exosome biogenesis, which involves formation endosomes cell membrane endocytosis, also gets packaged within along with DNA, RNA other proteins. Subsequently, intraluminal vesicles (ILVs) are formed following inward budding endosomal membrane, turning into multi-vesicle bodies (MVBs). Finally, MVBs fuse form exosomes. As result, can be secreted out cells lysosomal pathway as Extracellular (eCIRP). (eCIRP) implicated conditions, including sepsis, ischemia-reperfusion damage, lung injury, neuroinflammation, release In addition, interacts TLR4, TREM-1, IL-6R, therefore involved triggering immune inflammatory responses. Accordingly, eCIRP has been studied potential novel targets for disease therapy. C23 M3, polypeptides oppose binding receptors, beneficial numerous illnesses. Some natural molecules such Luteolin Emodin antagonize CIRP, play roles similar responses inhibit macrophage-mediated inflammation. This review aims provide better understanding on translocation secretion extracellular space mechanisms inhibitory diverse

Language: Английский

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