The role of NOD-like receptors in innate immunity

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Март 15, 2023

The innate immune system in vertebrates and invertebrates relies on conserved receptors ligands, pathways that can rapidly initiate the host response against microbial infection other sources of stress danger. Research into family NOD-like (NLRs) has blossomed over past two decades, with much being learned about ligands conditions stimulate NLRs outcomes NLR activation cells animals. play key roles diverse functions, ranging from transcription MHC molecules to initiation inflammation. Some are activated directly by their while may have indirect effects NLRs. New findings coming years will undoubtedly shed more light molecular details involved activation, as well physiological immunological ligation.

Язык: Английский

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Recent advances and evolving concepts in Still’s disease

Nature Reviews Rheumatology, Год журнала: 2024, Номер 20(2), С. 116 - 132

Опубликована: Янв. 11, 2024

Язык: Английский

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cGAS-STING, inflammasomes and pyroptosis: an overview of crosstalk mechanism of activation and regulation

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Янв. 9, 2024

Abstract Background Intracellular DNA-sensing pathway cGAS-STING, inflammasomes and pyroptosis act as critical natural immune signaling axes for microbial infection, chronic inflammation, cancer progression organ degeneration, but the mechanism regulation of crosstalk network remain unclear. Main body abstract Cellular stress disrupts mitochondrial homeostasis, facilitates opening permeability transition pore leakage DNA to cell membrane, triggers inflammatory responses by activating cGAS-STING signaling, subsequently induces activation onset pyroptosis. Meanwhile, inflammasome-associated protein caspase-1, Gasdermin D, CARD domain ASC potassium channel are involved in regulating pathway. Importantly, this has a cascade amplification effect that exacerbates immuno-inflammatory response, worsening pathological process autoimmune diseases. Given importance innate immunity, it is emerging new avenue explore mechanisms multiple disease pathogenesis. Therefore, efforts define strategies selectively modulate different settings have been or ongoing. In review, we will describe how mechanistic understanding driving possible therapeutics targeting network, focusing on interacting regulatory proteins, pathways, hub between inflammasomes, Short conclusion This review aims provide insight into roles pyroptosis, highlight some promising directions future research intervention.

Язык: Английский

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An overview of anti-SARS-CoV-2 and anti-inflammatory potential of baicalein and its metabolite baicalin: Insights into molecular mechanisms

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 258, С. 115629 - 115629

Опубликована: Июль 6, 2023

Язык: Английский

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Inflammasome Signaling, Thromboinflammation, and Venous Thromboembolism

JACC Basic to Translational Science, Год журнала: 2023, Номер 8(9), С. 1245 - 1261

Опубликована: Июнь 7, 2023

Venous thromboembolism (VTE) remains a major health burden despite anticoagulation advances, suggesting incomplete management of pathogenic mechanisms. The NLRP3 (NACHT-, LRR- and pyrin domain-containing protein 3) inflammasome, interleukin (IL)-1, pyroptosis are emerging contributors to the inflammatory pathogenesis VTE. Inflammasome pathway activation occurs in patients with In preclinical models, inflammasome signaling blockade reduces venous thrombogenesis vascular injury, that this therapeutic approach may potentially maximize benefits, protecting from VTE occurrence, recurrence, ensuing post-thrombotic syndrome. nonselective inhibitor colchicine anti-IL-1β agent canakinumab reduce atherothrombosis without increasing bleeding. Rosuvastatin primary thrombotic events at least part through lipid-lowering independent mechanisms, paving way targeted anti-inflammatory strategies This review outlines recent clinical evidence supporting role for thrombosis, discusses the, yet unexplored, potential modulating prevent manage

Язык: Английский

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NLRP3 inflammasome and interleukin-1 contributions to COVID-19-associated coagulopathy and immunothrombosis

Cardiovascular Research, Год журнала: 2023, Номер 119(11), С. 2046 - 2060

Опубликована: Май 30, 2023

Abstract Immunothrombosis—immune-mediated activation of coagulation—is protective against pathogens, but excessive immunothrombosis can result in pathological thrombosis and multiorgan damage, as severe coronavirus disease 2019 (COVID-19). The NACHT-, LRR-, pyrin domain-containing protein 3 (NLRP3) inflammasome produces major proinflammatory cytokines the interleukin (IL)-1 family, IL-1β IL-18, induces pyroptotic cell death. Activation NLRP3 pathway also promotes immunothrombotic programs including release neutrophil extracellular traps tissue factor by leukocytes, prothrombotic responses platelets vascular endothelium. occurs patients with COVID-19 pneumonia. In preclinical models, blockade restrains COVID-19-like hyperinflammation pathology. Anakinra, recombinant human IL-1 receptor antagonist, showed safety efficacy is approved for treatment hypoxaemic early signs hyperinflammation. non-selective inhibitor colchicine reduced hospitalization death a subgroup outpatients not COVID-19. Additional trials testing blockers are inconclusive or ongoing. We herein outline contribution to COVID-19-associated coagulopathy, review clinical evidence suggesting an engagement pathogenesis summarize current efforts target COVID-19, discuss challenges, unmet gaps, therapeutic potential that inflammasome-targeted strategies may provide inflammation-driven thrombotic disorders

Язык: Английский

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Inflammasome: structure, biological functions, and therapeutic targets

MedComm, Год журнала: 2023, Номер 4(5)

Опубликована: Окт. 1, 2023

Inflammasomes are a group of protein complex located in cytoplasm and assemble response to wide variety pathogen-associated molecule patterns, damage-associated cellular stress. Generally, the activation inflammasomes will lead maturation proinflammatory cytokines pyroptotic cell death, both associated with inflammatory cascade amplification. A sensor protein, an adaptor, procaspase interact through their functional domains compose one subunit inflammasome complex. Under physiological conditions, functions against pathogen infection endogenous dangers including mtROS, mtDNA, so on, while dysregulation its can unwanted results. In recent years, advances have been made clarify mechanisms activation, structural details them (negative/positive) multiple disease models animal human. The range stimuli makes function diverse Here, we review structure, biological functions, therapeutic targets inflammasomes, highlight NLRP3, NLRC4, AIM2 which most well studied. conclusion, this focuses on process, structure well-studied summarizing predicting approaches for treatment prevention as target. We aim provide fresh insight into new solutions challenges field.

Язык: Английский

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COVID-19 therapeutics

Clinical Microbiology Reviews, Год журнала: 2024, Номер 37(2)

Опубликована: Май 21, 2024

SUMMARYSince the emergence of COVID-19 in 2020, an unprecedented range therapeutic options has been studied and deployed. Healthcare providers have multiple treatment approaches to choose from, but efficacy those often remains controversial or compromised by viral evolution. Uncertainties still persist regarding best therapies for high-risk patients, drug pipeline is suffering fatigue shortage funding. In this article, we review antiviral activity, mechanism action, pharmacokinetics, safety therapies. Additionally, summarize evidence from randomized controlled trials on various antivirals discuss unmet needs which should be addressed.

Язык: Английский

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Necroptosis does not drive disease pathogenesis in a mouse infective model of SARS-CoV-2 in vivo

Cell Death and Disease, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 30, 2024

Abstract Necroptosis, a type of lytic cell death executed by the pseudokinase Mixed Lineage Kinase Domain-Like (MLKL) has been implicated in detrimental inflammation caused SARS-CoV-2 infection. We minimally and extensively passaged single clinical isolate to create models mild severe disease mice allowing us dissect role necroptosis pathogenesis. infected wild-type MLKL-deficient found no significant differences viral loads or lung pathology. In our model COVID-19, MLKL-deficiency did not alter host response, ameliorate weight loss, diminish systemic pro-inflammatory cytokines levels, prevent lethality aged animals. Our vivo indicate that is dispensable pathogenesis COVID-19.

Язык: Английский

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Therapeutic effects of tetrandrine in inflammatory diseases: a comprehensive review

Inflammopharmacology, Год журнала: 2024, Номер 32(3), С. 1743 - 1757

Опубликована: Апрель 3, 2024

Язык: Английский

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