Результаты поиска

Human endogenous retrovirus expression is inversely related with the up-regulation of interferon-inducible genes in the skin of patients with lichen planus.

Lichen planus (LP) is a common inflammatory skin disease of unknown etiology. Reports of a common transactivation of quiescent human endogenous retroviruses (HERVs) support the connection of viruses to the disease. HERVs are ancient retroviral sequences in the human genome and their transcription is often deregulated in cancer and autoimmune diseases. We explored the transcriptional activity of HERV sequences as well as the antiviral restriction factor and interferon-inducible genes in the skin from LP patients and healthy control (HC) donors. The study included 13 skin biopsies from patients

Genes involved in innate immunity associated with asbestos-related fibrotic changes.

OBJECTIVES: To determine whether genetic polymorphisms in several candidate genes related to innate immunity and protease-antiprotease balance modify individual susceptibility to develop asbestos-related fibrotic pleuropulmonary changes. METHODS: Sixteen polymorphisms from nine genes (NLRP3, CARD8, TNF, TGFB1, GC, MMP1, MMP9, MMP12 and TIMP2) were genotyped from 951 Finnish asbestos-exposed workers. The genotype/haplotype data were compared to signs of fibrosis and pleural thickenings using linear and logistic regression analysis adjusted for potential confounders. RESULTS: A functional poly

IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice.

BACKGROUND: The application of forces during orthodontic treatment can induce pulpal calcifications, characterized by the deposition of mineralized tissue in the pulp cavity space, there may be repercussions on dental procedures, especially endodontic treatment. The objective of this article is to map the scientific evidence and any gaps in knowledge regarding the relationship between orthodontics and dental pulp calcifications. MATERIAL AND METHODS: The study comprised a scoping review whose guiding question was: "What is the scientific evidence of the association between pulpal calcificatio

Immune inhibitory ligand CD200 induction by TLRs and NLRs limits macrophage activation to protect the host from meningococcal septicemia.

Macrophage activation is essential for protection against bacterial pathogens but needs to be regulated to prevent damage to the host. We show a key role for the immune inhibitory receptor CD200R and its ligand CD200 in the context of infection with the Gram-negative human pathogen Neisseria meningitidis. N. meningitidis induced CD200 but downregulated CD200R on macrophages in a manner dependent on Neisserial lipopolysaccharide, Toll-like receptor-4 (TLR-4), and the MyD88 pathway but independent of a known Neisserial receptor, scavenger receptor A (SR-A). Agonists of the pattern-recognition re

Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy.

Bortezomib, a first-generation proteasome inhibitor widely used in chemotherapy for hematologic malignancy, has effective anti-cancer activity but often causes severe peripheral neuropathy. Although bortezomib-induced peripheral neuropathy (BIPN) is a dose-limiting toxicity, there are no recommended therapeutics for its prevention or treatment. One of the most critical problems is a lack of knowledge about pathological mechanisms of BIPN. Here, we summarize the known mechanisms of BIPN based on preclinical evidence, including morphological abnormalities, involvement of non-neuronal cells, oxid

Совпадение в полном тексте источника
… Bortezomib causes an increase of NOD-like receptor family pyrin domain containing 3 (NLRP3) expression via enhancement of STAT3 binding to the promoter region of Nlrp3 , as well as STAT3-dependent acetylation of histone H3/H4 in that region [ 55 ]. … voltage-gated calcium channel 3.2 (Ca v 3.2); CC chemokine ligand 2 (CCL2); glutamate/aspartate transporter (GLAST); interleukin-6 (IL-6); c-Jun N-terminal kinase (JNK); nicotinamide adenine dinucleotide (NAD + ); nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB); NOD-like receptor family pyrin …

HMGB1: новая биомаркировка и лечебная цель аутоиммунной и аутовоспалительной кожных заболеваний.

Вставка 1 группы высокой подвижности (HMGB1) выражена почти во всех человеческих клетках. Во время активации клеток и клеточной смерти нуклеопротеин HMGB1 может перемещаться в внеклеточное пространство, тем самым посредничая ранним подстрекательским ответом как сигнализация или молекулярный рисунок, связанный с повреждением (DAMP). Внешнеклеточный HMGB1 взаимодействует с иммунными клетками, связываясь с системой распознавания рецепторов Toll-подобных (TLR), включая TLR2 и TLR4, и рецептором для современных продуктов для гликации (RAGE), тем самым содействуя иммунной реакции для защиты хоста от

Совпадение в полном тексте источника
… The secretion of HMGB1 is controlled by NLRP3 inflammasome activation in outer root sheath cells, which suggests that HMGB1 collaborates with IL-1β, an effector of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome, to promote inflammation in patients with AA ( 68 ). … The NLR family pyrin domain-containing 3 (NLRP3) inflammasome is activated in the outer hair root sheath cells of patients with alopecia areata. …

Inflammation in cancer: therapeutic opportunities from new insights.

As one part of the innate immune response to external stimuli, chronic inflammation increases the risk of various cancers, and tumor-promoting inflammation is considered one of the enabling characteristics of cancer development. Recently, there has been growing evidence on the role of anti-inflammation therapy in cancer prevention and treatment. And researchers have already achieved several noteworthy outcomes. In the review, we explored the underlying mechanisms by which inflammation affects the occurrence and development of cancer. The pro- or anti-tumor effects of these inflammatory factors

Совпадение в полном тексте источника
… Besides, GL-V9, an AMPK activator, prevents colorectal cancer associated with colitis by limiting the NLRP3, nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain-containing receptor (NLRP3) inflammasome through the process of autophagy [ 121 ]. …

Остеопонтин по хроническим воспламенительным болезням: механизмы, биомаркеры и терапевтические стратегии.

Хронические подстрекательские заболевания, такие, как ревматуидный артрит (RA), системный волчан Эрематосус (SLE), множественный склероз (MS), атеросклероз и воспалительный кишечник (IBD), вызывают серьезную озабоченность во всем мире. Эти расстройства характеризуются стойким воспалением, дисфункцией иммунной системы, повреждением тканей и фиброзом, что в конечном счете приводит к серьезной дисфункции органов и снижению качества жизни. Остеопонтин (OPS), многофункциональный внеклеточный белок, играет решающую роль в иммунном регулировании, воспалении и реконструкции тканей. Она поощряет набор

Совпадение в полном тексте источника
… OPN: osteopontin; PI3K/Akt: phosphatidylinositol 3-kinase/protein kinase B; MAPK: mitogen-activated protein kinase; ERK: extracellular signal-regulated kinase; JNK: c-Jun N-terminal kinase; NLRP3: NOD-like receptor family pyrin domain-containing 3; GSDMD: Gasdermin D; ER: Endoplasmic Reticulum; ATF4: … Abbreviations: OPN: osteopontin; PI3K/Akt: phosphatidylinositol 3-kinase/protein kinase B; MAPK: mitogen-activated protein kinase; ERK: extracellular signal-regulated kinase; JNK: c-Jun N-terminal kinase; NLRP3: NOD-like receptor family pyrin domain-containing 3; GSDMD: Gasdermin D; ER: Endoplasmic Reticulum …

Herniarin mitigates inflammation, oxidative stress, and apoptosis in experimental serous otitis media via NRF2/HO-1 and NLRP3/Caspase-1 pathways.

OBJECTIVE: Serous otitis media (SOM) is a prevalent inflammatory condition of the middle ear. Herniarin (7-methoxycoumarin) is a coumarin derivative with anti-inflammatory and antioxidant properties. This study aimed to investigate the therapeutic potential of herniarin against experimentally induced SOM in rats, focusing on the NRF2/HO-1 and NLRP3/Caspase-1 pathways. METHODS: Thirty six adult male Wistar rats were allocated into six groups (n = 6): Control, Herniarin 200 mg/kg, Otitis, Otitis + Herniarin 100 mg/kg, Otitis + Herniarin 200 mg/kg, and Otitis + Dexamethasone. SOM was induced by

A mechanism for hypoxia-induced inflammatory cell death in cancer.

Hypoxic cancer cells resist many antineoplastic therapies and can seed recurrence1,2. We previously found that either deficiency or inhibition of protein-tyrosine phosphatase (PTP1B) promotes human epidermal growth factor receptor 2-positive breast cancer cell death in hypoxia by activation of RNF213 (ref. 3), a large protein with multiple AAA-ATPase domains and two ubiquitin ligase domains (RING and RZ) implicated in Moyamoya disease, lipotoxicity and innate immunity4. Here we report that PTP1B and ABL1/2 reciprocally control RNF213 tyrosine phosphorylation and, consequently, its oligomerizat

MCC950 inhibits the inflammatory response and excessive proliferation of canine corneal stromal cells induced by Staphylococcus pseudintermedius.

BACKGROUND: The stromal layer is the thickest layer of the cornea, and corneal stromal cells play an important role in the inflammatory response and wound repair. This study investigated the effect of MCC950, an inhibitor of NLRP3 inflammasome, on the inflammatory response and proliferation of canine corneal stromal cells (CCSCs) induced by Staphylococcus pseudintermedius (S. pseudintermedius). METHODS: CCSCs were pretreated with MCC950 and infected with S. pseudintermedius. The phosphorylation of p65, IκBα, PI3K, and AKT and the expression of NLRP3, caspase-1 p20, cleaved IL-1β, ASC, β-caten

Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes.

Placental malaria (PM) is associated with severe inflammation leading to abortion, preterm delivery, and intrauterine growth restriction. Innate immunity responses play critical roles, but the mechanisms underlying placental immunopathology are still unclear. Here, we investigated the role of inflammasome activation in PM by scrutinizing human placenta samples from an endemic area and ablating inflammasome components in a PM mouse model. The reduction in birth weight in babies from infected mothers is paralleled by increased placental expression of AIM2 and NLRP3 inflammasomes. Using genetic d

Electroacupuncture preconditioning attenuates acute myocardial ischemia injury through inhibiting NLRP3 inflammasome activation in mice.

AIMS: Electro-acupuncture pretreatment (EAP) plays a protective role in myocardial ischemia (MI) injury. However, the underlying mechanism remains unclear. A growing body of evidence suggests postinfarction inflammatory response directly affects the remodeling of ventricular function. The purpose of this study was to investigate whether EAP alleviates MI through NLRP3 inflammasome inhibition. MATERIALS AND METHODS: We constructed an AMI model by ligating the left anterior descending (LAD) coronary artery after 3 days of EAP with C57BL/6 mice. Echocardiography and TTC staining were employed to

Pannexin 1 Channels Contribute to IL-1β Expression via NLRP3/Caspase-1 Inflammasome in Aspergillus Fumigatus Keratitis.

Purpose: Pannexin 1 channels are deemed to play important roles in inflammation. However, there is limited information regarding their roles in fungal infection diseases, especially fungal keratitis. This study aimed to investigate the role of pannexin 1 channels in Aspergillus fumigatus (A. fumigatus) keratitis. Materials and Methods: Mouse models or immortalized human corneal epithelial cells (HCECs) were infected with or without A. fumigatus for given time. The expression of pannexin 1 channels was tested by qPCR, western blot and immunofluorescence staining. Mice of A. fumigatus keratitis

FABP4/aP2 Regulates Macrophage Redox Signaling and Inflammasome Activation via Control of UCP2.

Obesity-linked metabolic disease is mechanistically associated with the accumulation of proinflammatory macrophages in adipose tissue, leading to increased reactive oxygen species (ROS) production and chronic low-grade inflammation. Previous work has demonstrated that deletion of the adipocyte fatty acid-binding protein (FABP4/aP2) uncouples obesity from inflammation via upregulation of the uncoupling protein 2 (UCP2). Here, we demonstrate that ablation of FABP4/aP2 regulates systemic redox capacity and reduces cellular protein sulfhydryl oxidation and, in particular, oxidation of mitochondria

Clinical and Molecular Phenotypes of Low-Penetrance Variants of NLRP3: Diagnostic and Therapeutic Challenges.

OBJECTIVE: Cryopyrin-associated periodic syndromes (CAPS) result from gain-of-function mutations in the NLRP3 gene, which causes excessive release of interleukin-1β (IL-1β) and systemic inflammation. While pathogenetic NLRP3 variant phenotypes are well-characterized, low-penetrance NLRP3 variants represent a significant clinical challenge. The aims of this study were to determine the clinical phenotype, the in vitro biologic phenotype, and the effect of anti-IL-1 treatment in patients with low-penetrance NLRP3 variants. METHODS: A multicenter study of consecutive symptomatic patients with low…

Ca2+ Signaling but Not Store-Operated Ca2+ Entry Is Required for the Function of Macrophages and Dendritic Cells.

Store-operated Ca(2+) entry (SOCE) through Ca(2+) release-activated Ca(2+) (CRAC) channels is essential for immunity to infection. CRAC channels are formed by ORAI1 proteins in the plasma membrane and activated by stromal interaction molecule (STIM)1 and STIM2 in the endoplasmic reticulum. Mutations in ORAI1 and STIM1 genes that abolish SOCE cause severe immunodeficiency with recurrent infections due to impaired T cell function. SOCE has also been observed in cells of the innate immune system such as macrophages and dendritic cells (DCs) and may provide Ca(2+) signals required for their functi

The cyclopentenone prostaglandin 15d-PGJ2 inhibits the NLRP1 and NLRP3 inflammasomes.

Inflammasomes are cytosolic protein complexes that respond to diverse danger signals by activating caspase-1. The sensor components of the inflammasome, often proteins of the nucleotide-binding oligomerization domain-like receptor (NLR) family, detect stress, danger stimuli, and pathogen-associated molecular patterns. We report that the eicosanoid 15-deoxy-Δ(12,14)-PGJ2 (15d-PGJ2) and related cyclopentenone PGs inhibit caspase-1 activation by the NLR family leucine-rich repeat protein (NLRP)1 and NLRP3 inflammasomes. This inhibition was independent of the well-characterized role of 15d-PGJ2 as

Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity.

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in the Western world. Twenty per cent of NAFLD individuals develop chronic hepatic inflammation (non-alcoholic steatohepatitis, NASH) associated with cirrhosis, portal hypertension and hepatocellular carcinoma, yet the causes of progression from NAFLD to NASH remain obscure. Here, we show that the NLRP6 and NLRP3 inflammasomes and the effector protein IL-18 negatively regulate NAFLD/NASH progression, as well as multiple aspects of metabolic syndrome via mo

CFTR I556V Variant Exacerbates Cigarette Smoke-Induced Airway Inflammation in COPD by Promoting NLRP3 Inflammasome Activation.

BACKGROUND AND OBJECTIVE: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are known to cause cystic fibrosis (CF), a condition that shares several pathophysiological pulmonary features with chronic obstructive pulmonary disease (COPD). Despite these similarities, the relationship between CFTR gene mutations and the risk of developing COPD remains unclear and poorly understood. METHODS: We employed exon sequencing to detect CFTR exon variations in 208 COPD patients and 100 control subjects with normal lung function. Subsequently, we applied the adenine base edi