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NOD like receptor

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https://www.readbyqxmd.com/read/29343269/microglial-activation-mediates-chronic-mild-stress-induced-depressive-and-anxiety-like-behavior-in-adult-rats
#1
Ya-Lin Wang, Qiu-Qin Han, Wen-Qing Gong, Dong-Hui Pan, Li-Zheng Wang, Wei Hu, Min Yang, Bing Li, Jin Yu, Qiong Liu
BACKGROUND: Depression is a heterogeneous disorder, with the exact neuronal mechanisms causing the disease yet to be discovered. Recent work suggests it is accompanied by neuro-inflammation, characterized, in particular, by microglial activation. However, microglial activation and its involvement in neuro-inflammation and stress-related depressive disorders are far from understood. METHODS: We utilized multiple detection methods to detect the neuro-inflammation in the hippocampus of rats after exposure to chronic mild stress (CMS)...
January 17, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29340626/suppression-of-nlrp3-inflammasome-by-oral-treatment-with-sulforaphane-alleviates-acute-gouty-inflammation
#2
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/29340077/lrp6-targeting-suppresses-gastric-tumorigenesis-via-p14arf-mdm2-p53-dependent-cellular-senescence
#3
Haibin Wang, Guoxing Xu, Zhengjie Huang, Weizheng Li, Huali Cai, Yunda Zhang, Disheng Xiong, Gang Liu, Shengjie Wang, Zengfu Xue, Qi Luo
NLRP6, a member of the Nod-like receptor family, protects against chemically induced intestinal injury and colitis-associated colon cancer. However, the cellular mechanisms involved in this NLRP6-mediated protection remain unclear. Here, we show that NLRP6 was down-regulated in approximately 75% of primary gastric cancer cases and exhibited significant associations with advanced clinical-stage lymph node metastasis and poor overall survival. Functional studies established that ectopic overexpression or down-regulation of NLRP6 inhibited cancer cell proliferation by inducing cell cycle arrest at the G1 phase via P21 and Cyclin D1 both in vitro and in vivo...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339259/perturbations-of-the-gut-microbiome-genes-in-infants-with-atopic-dermatitis-according-to-feeding-type
#4
Min-Jung Lee, Mi-Jin Kang, So-Yeon Lee, Eun Lee, Kangjin Kim, Sungho Won, Dong In Suh, Kyung Won Kim, Youn Ho Sheen, Kangmo Ahn, Bong-Soo Kim, Soo-Jong Hong
BACKGROUND: Perturbations of the infant gut microbiota can shape the development of the immune system and link to the risk of allergic diseases. OBJECTIVE: To understand the role of the gut microbiome in atopic dermatitis, the metagenome of the infant gut microbiome was analyzed according to feeding types. METHODS: The composition of gut microbiota was analyzed in fecal samples from 129 infants (6-month-old) by pyrosequencing, including 66 healthy infants and 63 infants with atopic dermatitis...
January 12, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29339053/upregulation-of-nlrp3-via-stat3-dependent-histone-acetylation-contributes-to-painful-neuropathy-induced-by-bortezomib
#5
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
#6
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/29330552/dosimetry-prediction-for-clinical-translation-of-64cu-pembrolizumab-immunopet-targeting-human-pd-1-expression
#7
Arutselvan Natarajan, Chirag B Patel, Frezghi Habte, Sanjiv S Gambhir
The immune checkpoint programmed death 1 receptor (PD-1) expressed on some tumor-infiltrating lymphocytes, and its ligand (PD-L1) expressed on tumor cells, enable cancers to evade the immune system. Blocking PD-1 with the monoclonal antibody pembrolizumab is a promising immunotherapy strategy. Thus, noninvasively quantifying the presence of PD-1 expression in the tumor microenvironment prior to initiation of immune checkpoint blockade may identify the patients likely to respond to therapy. We have developed a 64Cu-pembrolizumab radiotracer and evaluated human dosimetry...
January 12, 2018: Scientific Reports
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
#8
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/29316044/global-transcriptome-profiling-of-mild-relapsing-remitting-versus-primary-progressive-multiple-sclerosis
#9
Marcus W Koch, Yaroslav Ilnytskyy, Andrey Golubov, Luanne M Metz, V Wee Yong, Olga Kovalchuk
BACKGROUND: Genetic research in MS mostly compares MS patients with healthy controls, but does not differentiate between MS disease courses. We compared peripheral blood gene expression patterns between extremes of MS phenotypes: patients with mild relapsing-remitting MS (mRRMS) and primary progressive MS (PPMS). METHODS: We analyzed global gene expression profiles of peripheral blood samples of age and gender matched patients with mRRMS and PPMS. Detailed bioinformatic and gene set enrichment analysis, pathway and principle component analyses were used to identify differentially expressed genes and pathways...
January 8, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29312598/interleukin-22-participates-in-the-inflammatory-process-of-vitiligo
#10
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/29305119/weicao-capsule-ameliorates-renal-injury-through-increasing-autophagy-and-nlrp3-degradation-in-uan-rats
#11
Jiacai Hu, Hao Wu, Daochun Wang, Zhijie Yang, Lihua Zhuang, Na Yang, Junjun Dong
Uric acid nephropathy (UAN) is one of the most common metabolic diseases and leads to kidney damage. This study aimed to evaluate the effect of Weicao capsule on renal injury of UAN rats and to examine whether the mechanism was associated with induction of autophagy and degradation of nucleotide binding oligomerization domain (Nod)-like receptor (NLR) protein 3 (NLRP3) inflammasome. Sixty Sprague-Dawley rats were randomly allocated into 6 groups: Control, Model, Allopurinol, and Weicao (0.55/1.1/2.2 g/kg) group...
January 2, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29303910/involvement-of-nucleotide-binding-and-oligomerization-domain-like-receptors-in-the-intestinal-injury-of-severe-acute-pancreatitis-in-rats
#12
Shan Xu, Shuqing Wei, Yu Guo, Donglai Cui, Jinfeng Yao
OBJECTIVES: The aim of the study was to observe the role of nucleotide-binding and oligomerization domain (NOD)-like receptors (NLR) in intestine injury of severe acute pancreatitis (SAP) in rats. METHODS: Severe acute pancreatitis was induced by retrograde infusion of sodium taurocholate into the biliopancreatic duct. Rats were divided into the following 6 groups: sham operation, SAP treated with saline, and SAP treated with interleukin 1β (IL-1β)-converting enzyme inhibitor, killed at 6 or 12 hours after operation...
January 5, 2018: Pancreas
https://www.readbyqxmd.com/read/29296826/tlr5-signaling-in-murine-bone-marrow-induces-hematopoietic-progenitor-cell-proliferation-and-aids-survival-from-radiation
#13
Benyue Zhang, Damilola Oyewole-Said, Jun Zou, Ifor R Willliams, Andrew T Gewirtz
Administration of the bacterial protein flagellin to mice activates innate immune signaling that protects against an array of challenges, including ionizing radiation. Herein, we define the underlying mechanism for this protection. We report that flagellin treatment induces proliferation and mobilization of bone marrow cells that aid survival following irradiation. Specifically, treatment of mice or bone marrow cells ex vivo with flagellin induced Toll-like receptor 5 (TLR5)-dependent and NOD-like receptor C4-independent proliferation of Lin-Sca-1+Kit+ (LSK) cells, which includes both hematopoietic stem cells that provide long-term repopulation (LTR) and multipotent progenitor cells (MPPs) that transiently proliferate and differentiate into a range of blood cell types...
September 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295651/mcc950-the-selective-nlrp3-inflammasome-inhibitor-protects-mice-against-traumatic-brain-injury
#14
Saifudeen Ismael, Sanaz Nasoohi, Tauheed Ishrat
NNucleotide oligomerization domain (NOD)-like receptor protein-3 (NLRP3) inflammasome may intimately contribute to sustaining damage following traumatic brain injury (TBI). This study aims to examine whether specific modulation of NLPR3 inflammasome by MCC950, a novel selective NLRP3 inhibitor confers protection after experimental TBI. Unilateral cortical impact injury was induced in young adult C57BL/6 mice. MCC950 (50 mg/kg, i.p.) or saline was administration at 1 h and 3 h post TBI. Animals were tested for neurological function, and then sacrificed for edema at 24 or 72 h post TBI...
January 2, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29281815/the-nlr-protein-nlrp6-does-not-impact-gut-microbiota-composition
#15
Paul Lemire, Susan J Robertson, Heather Maughan, Ivan Tattoli, Catherine J Streutker, Jaye M Platnich, Daniel A Muruve, Dana J Philpott, Stephen E Girardin
NLRP6 is a Nod-like receptor expressed in the intestinal epithelium. Previous studies reported a protective role for NLRP6 against intestinal injury and colitis-associated carcinogenesis via the regulation and establishment of a healthy microbiota. However, these results were not obtained using littermate animals, leaving the possibility that the pro-colitogenic microbiota phenotype associated with knockout (KO) mice was stochastically acquired and genotype independent. Here, we analyzed the microbiota at three intestinal locations from Nlrp6-/- and wild-type (WT) littermates, either co-caged or individually caged after weaning...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29273951/neuroinflammatory-responses-in-alzheimer-s-disease
#16
REVIEW
Cira Dansokho, Michael Thomas Heneka
Neuroinflammatory responses in Alzheimer's disease (AD) are complex and not fully understood. They involve various cellular and molecular players and associate interaction between the central nervous system (CNS) and the periphery. Amyloid peptides within the senile plaques and abnormally phosphorylated tau in neurofibrillary tangles are able to initiate inflammatory responses, in brain of AD patients and in mouse models of this disease. The outcome of these responses on the pathophysiology of AD depends on several factors and can be either beneficial or detrimental...
December 22, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29259708/applications-of-reconstituted-inflammasomes-in-a-cell-free-system-to-drug-discovery-and-elucidation-of-the-pathogenesis-of-autoinflammatory-diseases
#17
REVIEW
Naoe Kaneko, Tomoyuki Iwasaki, Yuki Ito, Hiroyuki Takeda, Tatsuya Sawasaki, Shinnosuke Morikawa, Naoko Nakano, Mie Kurata, Junya Masumoto
The inflammasome, typically consisting of a Nod-like receptor, apoptosis-associated speck-like protein, and pro-caspase-1, has recently been identified as a huge intracellular complex, which plays a crucial role in interleukin-1 maturation or specific physiological functions. Two Nod-like receptors, such as nucleotide-binding oligomerization domains-containing protein (Nod)1 and Nod2, interact with the receptor-interacting protein serine-threonine kinase (RIPK)2 accompanied by Iκ-B kinase (IKK) complexes to construct the nodosome, leading to nuclear factor (NF)-κB activation...
2017: Inflammation and Regeneration
https://www.readbyqxmd.com/read/29258866/suppression-of-nlrp3-attenuates-hemorrhagic-transformation-after-delayed-rtpa-treatment-in-thromboembolic-stroke-rats-involvement-of-neutrophil-recruitment
#18
Zhiliang Guo, Shuhong Yu, Xin Chen, Ping Zheng, Ting Hu, Zhenhui Duan, Xiaoyun Liu, Qian Liu, Ruidong Ye, Wusheng Zhu, Xinfeng Liu
BACKGROUND: Inflammation and neutrophils play pivotal roles in hemorrhagic transformation (HT) after recombinant tissue plasminogen activator (rtPA) treatment in stroke; however, the contribution of Nod-like receptor protein 3 (NLRP3), a key component of the innate immune system, is not yet known. This study aimed to explore the role of NLRP3 in the delayed rtPA-induced HT and its association with the neutrophil recruitment. METHODS: Rats were subjected to thromboembolic focal cerebral ischemia and delayed rtPA treatment at 4 h after ischemia to mimic HT...
December 16, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29247991/function-and-regulation-of-il-1%C3%AE-in-inflammatory-diseases-and-cancer
#19
REVIEW
Ankit Malik, Thirumala-Devi Kanneganti
The interleukin (IL)-1 family of cytokines is currently comprised of 11 members that have pleiotropic functions in inflammation and cancer. IL-1α and IL-1β were the first members of the IL-1 family to be described, and both signal via the same receptor, IL-1R. Over the last decade, much progress has been made in our understanding of biogenesis of IL-1β and its functions in human diseases. Studies from our laboratory and others have highlighted the critical role of nod-like receptors (NLRs) and multi-protein complexes known as inflammasomes in the regulation of IL-1β maturation...
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
#20
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
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