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https://www.readbyqxmd.com/read/29345311/calcium-sensing-receptor-activates-the-nlrp3-inflammasome-in-ls14-preadipocytes-mediated-by-erk1-2-signaling
#1
Amanda D'Espessailles, Yuly A Mora, Cecilia Fuentes, Mariana Cifuentes
The study of the mechanisms that trigger inflammation in adipose tissue is key to understanding and preventing the cardiometabolic consequences of obesity. We have proposed a model where activation of the G protein-coupled calcium sensing receptor (CaSR) leads to inflammation and dysfunction in adipose cells. Upon activation, CaSR can mediate the expression and secretion of proinflammatory factors in human preadipocytes, adipocytes and adipose tissue explants. One possible pathway involved in CaSR-induced inflammation is the activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome, that promotes maturation and secretion of interleukin (IL)-1β...
January 18, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29344132/aberrant-nlrp3-inflammasome-associated-with-aryl-hydrocarbon-receptor-potentially-contributes-to-the-imbalance-of-t-helper-cells-in-patients-with-acute-myeloid-leukemia
#2
Yan Jia, Chen Zhang, Mingqiang Hua, Min Wang, Ping Chen, Daoxin Ma
Acute myeloid leukemia (AML) is a hematological malignancy in which the immune response serves a pivotal role in progression. Aryl hydrocarbon receptor (AHR) is involved in the modulation of the immune system, particularly in the differentiation of T-helper cell (Th) subsets. Although the NLR family pyrin domain-containing 3 (NLRP3) inflammasome has been implicated as essential in the pathogenesis of autoimmune and inflammatory diseases, the role it serves in the development of AML remains unknown. Therefore, in order to identify and describe the possible roles of AHR, as well as NLRP3 inflammasome, in the pathogenesis of AML and their relationship with Th subsets (Th1 Th22), the present study investigated the mRNA expression levels of AHR and NLRP3 inflammasome molecules in the peripheral blood and bone marrow...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29340626/suppression-of-nlrp3-inflammasome-by-oral-treatment-with-sulforaphane-alleviates-acute-gouty-inflammation
#3
Gabsik Yang, Sang Hyeon Yeon, Hye Eun Lee, Han Chang Kang, Yong Yeon Cho, Hye Suk Lee, Joo Young Lee
Objective: The aetiology of gout is closely linked to the deposition of monosodium uric acid (MSU) crystals and the consequent activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we investigated whether oral administration of an NLRP3 inhibitor would be effective to attenuate the symptoms of gout. Methods: The effects of oral administration with sulforaphane (SFN) were examined in two mouse models of acute gout induced by injection of MSU crystals into footpads or air pouch...
January 10, 2018: Rheumatology
https://www.readbyqxmd.com/read/29339053/upregulation-of-nlrp3-via-stat3-dependent-histone-acetylation-contributes-to-painful-neuropathy-induced-by-bortezomib
#4
Cui-Cui Liu, Zhu-Xi Huang, Xiao Li, Kai-Feng Shen, Meng Liu, Han-Dong Ouyang, Su-Bo Zhang, Yu-Ting Ruan, Xiao-Long Zhang, Shao-Ling Wu, Wen-Jun Xin, Chao Ma
Painful neuropathy, as a severe side effect of chemotherapeutic bortezomib, is the most common reason for treatment discontinuation. However, the mechanism by which administration of bortezomib leads to painful neuropathy remains unclear. In the present study, we found that application of bortezomib significantly increased the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and phosphorylated signal transducer and activator of transcription-3 (STAT3) in dorsal root ganglion (DRG). Intrathecal injection of NLRP3 siRNA significantly prevented the mechanical allodynia induced by bortezomib treatment, and intrathecal injection of recombinant adeno-associated virus vector encoding NLRP3 markedly decreased paw withdrawal threshold of naive rats...
January 12, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29338910/synthesis-of-deuterium-labelled-analogues-of-nlrp3-inflammasome-inhibitor-mcc950
#5
Manohar Salla, Mark S Butler, Nicholas L Massey, Janet C Reid, Matthew A Cooper, Avril A B Robertson
This study describes the syntheses of di, tetra and hexa deuterated analogues of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome inhibitor MCC950. In di and tetra deuterated analogues, deuteriums were incorporated into the 1,2,3,5,6,7-hexahydro-s-indacene moiety, whereas in the hexa deuterated MCC950 deuteriums were incorporated into the 2-(furan-3-yl)propan-2-ol moiety. The di deuterated MCC950 analogue was synthesised from 4-amino-3,5,6,7-tetrahydro-s-indacen-1(2H)-one 5. Tetra deuterated analogues were synthesised in 10 chemical steps starting with 5-bromo-2,3-dihydro-1H-inden-1-one 9, whereas the hexa deuterated analogue was synthesised in four chemical steps starting with ethyl-3-furoate 24...
December 26, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29329362/clostridium-butyricum-regulates-visceral-hypersensitivity-of-irritable-bowel-syndrome-by-inhibiting-colonic-mucous-low-grade-inflammation-through-its-action-on-nlrp6
#6
Kejia Zhao, Leimin Yu, Xi Wang, Yibo He, Bin Lu
Visceral hypersensitivity induced by stress is quite common in irritable bowel syndrome (IBS) patients. Probiotics play an important role in reducing visceral hypersensitivity in IBS patients. However, the mechanism has not been clearly elucidated. In this study, we investigated the role of nod-like receptor pyrin domain-containing protein 6 (NLRP6) in Clostridium butyricum-regulated IBS induced by stress. Our results showed that NLRP6 was down-regulated in IBS group colon tissues. In addition, IL-18, IL-1β, myeloperoxidase (MPO), d-lactic acid (D-LA), and CD172a were up-regulated in the IBS group of colonic mucous...
January 10, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29321274/irf1-is-a-transcriptional-regulator-of-zbp1-promoting-nlrp3-inflammasome-activation-and-cell-death-during-influenza-virus-infection
#7
Teneema Kuriakose, Min Zheng, Geoffrey Neale, Thirumala-Devi Kanneganti
Innate immune sensing of influenza A virus (IAV) induces activation of various immune effector mechanisms, including the nucleotide and oligomerization domain, leucine-rich repeat-containing protein family, pyrin domain containing 3 (NLRP3) inflammasome and programmed cell death pathways. Although type I IFNs are identified as key mediators of inflammatory and cell death responses during IAV infection, the involvement of various IFN-regulated effectors in facilitating these responses are less studied. In this study, we demonstrate the role of IFN regulatory factor (IRF)1 in promoting NLRP3 inflammasome activation and cell death during IAV infection...
January 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29319163/microrna-22-suppresses-cell-proliferation-migration-and-invasion-in-oral-squamous-cell-carcinoma-by-targeting-nlrp3
#8
Xiaodong Feng, Qingqiong Luo, Han Wang, Han Zhang, Fuxiang Chen
MicroRNAs (miRNAs) have been implicated as important regulators of carcinogenesis and tumor development. Recently, microRNA-22 (miR-22) has been reported to be a cancer-related miRNA in several types of tumors. In this study, we aimed to investigate the role of miR-22 in oral squamous cell carcinoma (OSCC). We found that miR-22 expression was significantly decreased in OSCC tissues compared with that in the adjacent noncancerous tissues. Furthermore, lentivirus-mediated miR-22 overexpression markedly reduced OSCC cell viability, migration and invasion, whereas miR-22 inhibitor promoted these parameters...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29312598/interleukin-22-participates-in-the-inflammatory-process-of-vitiligo
#9
Jinjin Dong, Xiaohong An, Hui Zhong, Yichuan Wang, Jing Shang, Jia Zhou
Vitiligo is an acquired depigmentary skin inflammatory disorder. The pathogenesis of inflammatory skin disease involves the release of cytokines from keratinocytes, including interleukin (IL)-1β. IL-22 belongs to a family of cytokines structurally related to IL-10, including IL-19, IL-20, IL-24, and IL-26. In contrast to IL-10, IL-22 has proinflammatory activities. Among skin cell populations only keratinocytes are the major targets of IL-22. In the present study, we demonstrated that IL-22 promoting IL-1β secretion from keratinocytes via the Reactive oxygen species (ROS)-NOD-like receptor family, pyrin domain containing 3 (NLRP3)-caspase-1 pathway...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29304864/hypercapnia-induces-il-1%C3%AE-overproduction-via-activation-of-nlrp3-inflammasome-implication-in-cognitive-impairment-in-hypoxemic-adult-rats
#10
Hong-Guang Ding, Yi-Yu Deng, Ren-Qiang Yang, Qiao-Sheng Wang, Wen-Qiang Jiang, Yong-Li Han, Lin-Qiang Huang, Miao-Yun Wen, Wen-Hong Zhong, Xu-Sheng Li, Fan Yang, Hong-Ke Zeng
BACKGROUND: Cognitive impairment is one of common complications of acute respiratory distress syndrome (ARDS). Increasing evidence suggests that interleukin-1 beta (IL-1β) plays a role in inducing neuronal apoptosis in cognitive dysfunction. The lung protective ventilatory strategies, which serve to reduce pulmonary morbidity for ARDS patients, almost always lead to hypercapnia. Some studies have reported that hypercapnia contributes to the risk of cognitive impairment and IL-1β secretion outside the central nervous system (CNS)...
January 5, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29301940/the-nlr-family-pyrin-domain-containing-11-protein-contributes-to-the-regulation-of-inflammatory-signalling
#11
Kornelia Ellwanger, Emily Becker, Ioannis Kienes, Anna Sowa, Yvonne Postma, Yamel Cardona Gloria, Alexander N R Weber, Thomas A Kufer
Mammalian NLR proteins contribute to the regulation and induction of innate and adaptive immunity in mammals although the function of about half of the currently identified NLR proteins remains poorly characterized. Here we analysed the function of the primate-specific NLRP11 gene product. We show that NLRP11 is highly expressed in immune cells, including myeloid cells, B cells and some B cell lymphoma lines. Overexpression of NLRP11 in human cells did not trigger key innate immune signalling pathways including NF-κB and type I interferon responses...
January 4, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29285164/resveratrol-alleviates-staphylococcus-aureus-pneumonia-by-inhibition-of-the-nlrp3-inflammasome
#12
Suxia Wu, Jianan Huang
Staphylococcus aureus (S. aureus) causes a wide variety of infections, including S. aureus pneumonia. Resveratrol, a natural polyphenolic compound contained in several plant species, exerts various activities, including anti-bacterial and pulmonary protective activities. The aim of the present study was to evaluate the protective effect of resveratrol on a murine model of S. aureus pneumonia and to elucidate the underlying mechanisms. It was found that resveratrol significantly reduced S. aureus-induced mortality, ameliorated lung injury and decreased cytokine levels in the bronchoalveolar lavage fluid and lung tissue of S...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29277561/nuclear-receptor-subfamily-1-group-d-member-1-regulates-circadian-activity-of-nlrp3-inflammasome-to-reduce-the-severity-of-fulminant-hepatitis-in-mice
#13
B Pourcet, M Zecchin, L Ferri, J Beauchamp, S Sitaula, C Billon, S Delhaye, J Vanhoutte, A Mayeuf-Louchart, Q Thorel, J Haas, J Eeckhoute, D Dombrowicz, C Duhem, A Boulinguiez, S Lancel, Y Sebti, T Burris, B Staels, H Duez
BACKGROUND & AIMS: The innate immune system responds not only to bacterial signals, but also to non-infectious danger-associated molecular patterns that activate the NLRP3 inflammasome complex after tissue injury. Immune functions vary over the course of the day, but it is not clear whether these changes affect the activity of the NLRP3 inflammasome. We investigated whether the core clock component nuclear receptor subfamily 1 group D member 1 (NR1D1, also called Rev-erbα) regulates expression, activity of the NLRP3 inflammasome, and its signaling pathway...
December 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29276519/quaking-deficiency-amplifies-inflammation-in-experimental-endotoxemia-via-the-aryl-hydrocarbon-receptor-signal-transducer-and-activator-of-transcription-1-nf-%C3%AE%C2%BAb-pathway
#14
Li Wang, Dong-Sheng Zhai, Ban-Jun Ruan, Cheng-Ming Xu, Zi-Chen Ye, Huan-Yu Lu, Ying-Hao Jiang, Zhen-Yu Wang, An Xiang, Yuan Yang, Jian-Lin Yuan, Zi-Fan Lu
Macrophages, characterized by considerable diversity and plasticity, play a crucial role in a broad spectrum of biological processes, including inflammation. However, the molecular mechanisms underlying the diverse phenotypes of macrophages are not well defined. Here, we show that the RNA-binding protein, quaking (QKI), dynamically modulates macrophage polarization states. After lipopolysaccharide (LPS) stimulation, QKI-silenced RAW 264.7 cells displayed a pro-inflammatory M1 phenotype characterized by increased expression of iNOS, TNF-α, and IL-6 and decreased expression of anti-inflammatory factors, such as IL-10, found in inflammatory zone (Fizz1), and chitinase-like 3 (Chil3 or Ym1)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29273596/dihydrolipoic-acid-inhibits-lysosomal-rupture-and-nlrp3-through-lysosome-associated-membrane-protein-1-calcium-calmodulin-dependent-protein-kinase-ii-tak1-pathways-after-subarachnoid-hemorrhage-in-rat
#15
Keren Zhou, Budbazar Enkhjargal, Zhiyi Xie, Chengmei Sun, Lingyun Wu, Jay Malaguit, Sheng Chen, Jiping Tang, Jianmin Zhang, John H Zhang
BACKGROUND AND PURPOSE: The NLRP3 (nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3) inflammasome is a crucial component of the inflammatory response in early brain injury after subarachnoid hemorrhage (SAH). In this study, we investigated a role of dihydrolipoic acid (DHLA) in lysosomal rupture, NLRP3 activation, and determined the underlying pathway. METHODS: SAH was induced by endovascular perforation in male Sprague-Dawley rats...
January 2018: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29247997/the-nlrc4-inflammasome
#16
REVIEW
Joseph A Duncan, Scott W Canna
15 years ago, the fundamental biology of an inflammatory signaling complex eventually dubbed "the inflammasome" began to unravel in chronologic parallel with the discovery that many inflammatory diseases were associated with its hyperactivity. Though the genetic origins of Familial Mediterranean Fever (FMF, caused my mutations in MEFV) were discovered first, it would take nearly two decades before the mechanistic connections to a PYRIN inflammasome were made. In the interim, the intensive study of the NLRP3 inflammasome, and the diseases associated with its hyperactivation, have largely dictated the paradigm of inflammasome composition and function...
January 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29246797/il-1%C3%AE-production-by-intermediate-monocytes-is-associated-with-immunopathology-in-cutaneous-leishmaniasis
#17
Daniela Santos, Taís M Campos, Maíra Saldanha, Sergio C Oliveira, Mauricio Nascimento, Dario S Zamboni, Paulo R Machado, Sérgio Arruda, Phillip Scott, Edgar M Carvalho, Lucas P Carvalho
Cutaneous leishmaniasis due to Leishmania braziliensis infection is an inflammatory disease which skin ulcer development is associated with mononuclear cells infiltrate and high levels of inflammatory cytokines production. Recently, NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and IL-1β production has been associated with increased pathology in murine cutaneous leishmaniasis. We hypothesized that cutaneous leishmaniasis patients have increased expression of NLRP3 leading to high levels of IL-1β production...
December 12, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29235163/ultraviolet-b-eye-irradiation-aggravates-atopic-dermatitis-via-acth-and-nlrp3-inflammasome-in-nc-nga-mice
#18
Keiichi Hiramoto, Yurika Yamate, Satoshi Yokoyama
BACKGROUND: Ultraviolet (UV) B irradiation has been shown to improve atopic dermatitis (AD). However, the relationship between UVB eye irradiation and AD is not known. This issue was addressed using a mouse model of AD. METHODS: The eyes of NC/Nga mice were irradiated with UVB at a dose of 1.0 kJ/m2 using a 20SE sunlamp for the duration of the experimental period. RESULTS: AD symptoms deteriorated upon UVB eye irradiation. The levels of adrenocorticotropic hormone (ACTH) in the plasma and nucleotide-binding domain and leucine-rich-containing family, pyrin domain-containing (NLRP)3 and neutrophil markers in the skin were increased in UVB-irradiated mice...
December 13, 2017: Photodermatology, Photoimmunology & Photomedicine
https://www.readbyqxmd.com/read/29234126/epidermal-cornification-is-preceded-by-the-expression-of-a-keratinocyte-specific-set-of-pyroptosis-related-genes
#19
Julia Lachner, Veronika Mlitz, Erwin Tschachler, Leopold Eckhart
The homeostasis of the epidermis depends on keratinocyte differentiation and cornification, a mode of programmed cell death that does not elicit inflammation. Here, we report that cornification is associated with the expression of specific genes that control multiple steps of pyroptosis, another form of cell death that involves the processing and release of interleukin-1 family (IL1F) cytokines. Expression levels of pro-inflammatory IL1A and IL1B and of the pyroptotic pore-forming gasdermin (GSDM) D were downregulated during terminal differentiation of human keratinocytes in vitro...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29212744/selective-nlrp3-pyrin-domain-containing-protein-3-inflammasome-inhibitor-reduces-brain-injury-after-intracerebral-hemorrhage
#20
Honglei Ren, Ying Kong, Zhijia Liu, Dongyun Zang, Xiaoxia Yang, Kristofer Wood, Minshu Li, Qiang Liu
BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating disease without effective treatment. As a key component of the innate immune system, the NOD-like receptor (NLR) family, NLRP3 (pyrin domain-containing protein 3) inflammasome, when activated after ICH, promotes neuroinflammation and brain edema. MCC950 is a potent, selective, small-molecule NLRP3 inhibitor that blocks NLRP3 activation at nanomolar concentrations. Here, we examined the effect of MCC950 on brain injury and inflammation in 2 models of ICH in mice...
December 6, 2017: Stroke; a Journal of Cerebral Circulation
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