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The systemic autoinflammatory diseases: inborn errors of the innate immune system.

The autoinflammatory syndromes are a newly recognized group of immune disorders that lack the high titers of self-reactive antibodies and T cells characteristic of classic autoimmune disease. Nevertheless, patients with these illnesses experience unprovoked inflammatory disease in the absence of underlying infection. Here we discuss recent advances in eight Mendelian autoinflammatory diseases. The causative genes and the proteins they encode play a critical role in the regulation of innate immunity. Both pyrin and cryopyrin, the proteins mutated in familial Mediterranean fever and the cryopyri

Porcine Deltacoronavirus M Protein Binds NLRP3 to Promote Inflammasome Assembly via Competition with TRIM31.

Porcine deltacoronavirus (PDCoV) infection induces severe intestinal inflammation and acute diarrhea in piglets, resulting substantial economic losses. The NLR family pyrin domain containing 3 (NLRP3) inflammasome, a key component of the innate immune system, drives interleukin (IL)-1β maturation, and its excessive activation is closely linked to viral pathogenesis. However, its role in PDCoV infection remains unclear. Here, we report that PDCoV infection induces IL-1β maturation through NLRP3 inflammasome activation both in vivo and in vitro, and the M protein promotes NLRP3 inflammasome asse…

Nucleoside analog kamuvudine-9 показывает защитную и терапевтическую эффективность в мышиной модели множественного склероза.

Врожденный иммунный сигнал с помощью воспламенительной активации был причастен к патогенезу множественного склероза (MS). Ранее мы продемонстрировали, что ингибиторы обратной транскриптазы (NTIs), лекарства, утвержденные для лечения ВИЧ и гепатита В, и камувудины, более безопасные производные NRTI, оба препятствуют воспалению. Здесь мы сообщаем, что в экспериментальной аутоиммунной энцефалитной модели MS лечение камувудин-9 (K-9) производной NRTI с улучшенным профилем безопасности предотвратило дальнейшие неврологические недостатки и обратило вспять существовавший ранее паралич и потерю зрения

Совпадение в аннотации оригинала
Innate immune signaling through inflammasome activation has been implicated in the pathogenesis of multiple sclerosis (MS). We previously de … (NfL) chain. K-9 disrupted interactions between nucleotide-binding domain leucine-rich repeat (NLR) pyrin domain-containing protein 3 (NLRP3) and NIMA-related kinase 7 (NEK7) and between NLRP3 and NLR CARD domain containing 4 (NLRC4), inhibiting dual inflammasome activation. K-9 also exhibited appropriate safety and pharmacokinetic characteristics and biodistr …

Dehydrocostus Lactone Effectively Alleviates Inflammatory Diseases by Covalently and Irreversibly Targeting NLRP3.

The activation of nucleotide oligomerization domain-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is implicated in the pathogenesis of various inflammatory diseases. The natural product oridonin possesses a novel mechanism for NLRP3 inhibition and a unique binding mode with NLRP3, but its poor anti-inflammatory activity limits further application. After virtual screening of diverse natural product libraries, dehydrocostus lactone (DCL) was considered as a potential NLRP3 inhibitor. DCL effectively inhibited caspase-1 cleavage and release of IL-1β in mouse a…

Triggers of NLRC4 and AIM2 inflammasomes induce porcine IL-1β secretion.

Pigs are an important livestock and serve as a large animal model due to physiological and anatomical similarities with humans. Thus, components of the porcine immune system such as inflammasomes need to be characterized for disease control, vaccination, and translational research purposes. Previously, we and others elucidated porcine nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family Pyrin domain containing 3 (NLRP3) inflammasome activation. However, until now, porcine NLR family caspase recruitment domain (CARD)-containing 4 (NLRC4) and absent in melanoma 2 (AIM2) inf…

Activation of NLRP3 inflammasome in human middle ear cholesteatoma and chronic otitis media.

CONCLUSIONS: The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays an important role in the patho … f NLRP3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain and a pyrin domain), and caspase-1 in middle ear tissues in patients with cholesteatoma or chronic otitis media. METHODS: Middle ear tissue samples were obtained from patients with cholesteatoma or chronic otitis media. Control middle ear samples were collected durin …

YTHDF2 alleviates diabetic cardiomyopathy by targeting m6A-mediated degradation of lncRNA RMRP and inhibiting NLRP3-dependent pyroptosis.

Diabetic cardiomyopathy (DCM) poses a significant threat to diabetic patients, with NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation playing a critical role. In this research, we identified a previously unrecognized molecular pathway that contributed to DCM pathogenesis, mediated by the long non-coding RNA component of mitochondrial RNA processing endoribonuclease (lncRNA RMRP) and the m6A-recognizing protein YTH domain family protein 2 (YTHDF2). Our data demonstrated a marked elevation in lncRNA RMRP expression in both cardiomyocytes exposed to high glucose (…

Inhibition of focal adhesion kinase impairs tumor formation and preserves hearing in a murine model of NF2-related schwannomatosis.

NF2 (neurofibromatosis type 2)-related schwannomatosis (NF2-SWN) is a cancer predisposition syndrome characterized by the development of bil … es nucleotide-binding oligomerization domain-containing protein 2-, leucine rich repeats (LRR)- and pyrin domain-containing protein 3 inflammasome activation, and suppresses the hepatocyte growth factor-MET axis. Pharmacological inhibition of FAK with single agent VS-4718 did not significantly reduce macroscopic tumor volume; however, its use in combination wi …

Targeting of NLRP3 Gln624/Ser658 by Carabrone attenuates inflammatory diseases.

The NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome plays a crucial role in host defense; however, its aberrant activation leads to excessive release of pro-inflammatory cytokines, triggering inflammatory responses and tissue damage in human diseases. In this study, the inhibitory effect and anti-inflammatory potential of carabrone on the NLRP3 inflammasome were systematically evaluated. Carabrone suppressed lipopolysaccharide (LPS) + ATP/Nigericin-induced IL-1β secretion, Caspase-1 activation, and apoptosis-associated speck-like protein (ASC) speck formation. M…

Mechanisms and Targeted Therapeutic Strategies in Sepsis-Induced Myocardial Dysfunction: The Role of NLRP3 Inflammasome-Mediated Inflammation.

Sepsis is a systemic inflammatory response syndrome triggered by infection, in which excessive immune responses can lead to multiple organ f … s and modulating inflammation is the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3(NLRP3) inflammasome. This study aims to explore the role of the NLRP3 inflammasome in the pathogenesis of SIMD, with a focus on its involvement through pathways such as pyroptosis, oxidative stress, autophagy, mitochondrial damage, exos …

Circular RNAs: Regulators of endothelial cell dysfunction in atherosclerosis.

Endothelial cell (EC) dysfunction is associated with atherosclerosis. Circular RNAs (circRNAs) are covalently closed loops formed by back-splicing, are highly expressed in a tissue-specific or cell-specific manner, and regulate ECs mainly through miRNAs (mircoRNAs) or protein sponges. This review describes the regulatory mechanisms and physiological functions of circRNAs, as well as the differential expression of circRNAs in aberrant ECs. This review focuses on their roles in inflammation, proliferation, migration, angiogenesis, apoptosis, senescence, and autophagy in ECs from the perspective

Pathologically high intraocular pressure induces mitochondrial dysfunction through Drp1 and leads to retinal ganglion cell PANoptosis in glaucoma.

Glaucoma is a common neurodegenerative disease characterized by progressive retinal ganglion cell (RGC) loss and visual field defects. Patho … y modulating caspase3-dependent, nucleotide-binding oligomerization domain-like receptor-containing pyrin domain 3(NLRP3)-dependent, and receptor-interacting protein (RIP)-dependent pathways in the ph-IOP model. Overall, our findings provide new insights into possible protective interventions that could regulate mitochondrial dynamics to improve RGC survival.

Ageing related thyroid deficiency increases brain-targeted transport of liver-derived ApoE4-laden exosomes leading to cognitive impairment.

Alzheimer's disease (AD) is the prevalent cause of dementia in the ageing world population. Apolipoprotein E4 (ApoE4) allele is the key gene … nto the brain, where ApoE4 activated nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome by increasing cholesterol level in neural cells. This, in turn, affected cognition, locomotion and mood. Our study reveals pathological potential of exosomes-mediated relocation of ApoE4 from the periphery to the br …

Schnitzler syndrome and Schnitzler-like syndromes.

Schnitzler syndrome is a rare disease of adult-onset with main features including chronic urticarial rash, recurrent fever, arthralgia or ar … ction mutation of NLRP3 (nucleotide-binding oligomerization domain [NOD]-like receptor [NLR] family pyrin domain containing 3) gene in some patients with Schnitzler-like syndromes. Inflammasome activation is evident in patients with classical Schnitzler syndrome although no NLRP3 gene mutation is identified. Collectively, Schnitzler syndrome and Schnitzler-lik …

ККУ950 в отношении NLRP3-mediated - подстрекательские заболевания: последние данные и результаты лечения.

Имеющиеся данные свидетельствуют о том, что различные компоненты врожденной иммунной системы участвуют в патологических провокационных условиях. Среди этих компонентов семейство пиринов НЛР содержит 3 (NLRP3) в качестве воспламенителя может участвовать в разрушительных подстрекательских действиях путем стимулирования производства активной формы подстрекательских цитокинов. NLRP3 может быть задействована в патогенезе нескольких подстрекательских и аутоиммунных заболеваний, таких, как тип 2 - диабет, множественный склероз (MS), атеросклероз, болезнь Альцгеймера (AD), периодический синдром, связа

Совпадение в аннотации оригинала
Evidence suggests that various innate immune system components are involved in pathological inflammatory conditions. Among these components, the NLR family pyrin domain containing 3 (NLRP3) as an inflammasome can participate in destructive inflammatory responses by inducing the production of the active form of inflammatory cytokines. The NLRP3 could be invol…

Investigating the possible association between NLRP3 gene polymorphisms and myasthenia gravis.

INTRODUCTION: In this case-control study, we investigated the association between nucleotide oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) single-nucleotide polymorphisms (SNPs) rs10754558, rs3806265, rs4612666, and rs35829419 and myasthenia gravis (MG). METHODS: Samples from MG patients were selected from a previous study conducted in our neuromuscular clinic, which investigated the association between human leukocyte antigen (HLA) class II genes and MG. Genetic data of controls were also available from another study. The NLRP3 SNPs genotyping was performed us…

Agomelatine Exerts an Anti-inflammatory Effect by Inhibiting Microglial Activation Through TLR4/NLRP3 Pathway in pMCAO Rats.

Cerebral ischemic stroke is one of the main causes of death and long-term disability worldwide. However, the mechanism is unclear, and treat … (NF-κB) pathway components together with nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome components. In addition, agomelatine suppressed microglial activation and pyroptotic cell death after cerebral ischemic injury. These results suggest that agomelatine exerts an anti-inflammatory effect and attenuate …

Macrophage β2-Integrins Regulate IL-22 by ILC3s and Protect from Lethal Citrobacter rodentium-Induced Colitis.

β2-integrins promote neutrophil recruitment to infected tissues and are crucial for host defense. Neutrophil recruitment is defective in leukocyte adhesion deficiency type-1 (LAD1), a condition caused by mutations in the CD18 (β2-integrin) gene. Using a model of Citrobacter rodentium (CR)-induced colitis, we show that CD18-/- mice display increased intestinal damage and systemic bacterial burden, compared to littermate controls, ultimately succumbing to infection. This phenotype is not attributed to defective neutrophil recruitment, as it is shared by CXCR2-/- mice that survive CR infection. C

Microarray and whole-exome sequencing analysis of familial Behçet's disease patients.

Behçet's disease (BD), a chronic systemic inflammatory disorder, is characterized by recurrent oral and genital mucous ulcers, uveitis, and … r-associated kinase 4 (IRAK4), nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 14 (NRP14) and melanoma antigen-encoding gene E2 (MAGEE2); IRAK4 harbors a missense mutation, whereas NRP14 and MAGEE2 harbor nonsense mutations. These SNVs may serve as genetic markers that characterize BD.

[Clinical and genetic analysis of a family with autosomal dominant-familial Mediterranean fever].

OBJECTIVE: To analyze a pathogenic variant of MEFV gene in a family with autosomal dominant-familial Mediterranean fever (AD-FMF). METHODS: A 5-year-old boy presented with recurrent aseptic meningitis and his major symptoms included recurrent fever with headache and vomiting. His family members including his mother, sister and brother also had recurrent fever. A genetic disease was considered. DNAs were extracted from patient and all his family members' blood samples. Whole exome sequencing was performed to identify putative pathogenic variants that can explain this family's condition and San