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https://www.readbyqxmd.com/read/29778503/autoinflammatory-mutation-in-nlrc4-reveals-an-lrr-lrr-oligomerization-interface
#1
Fiona Moghaddas, Ping Zeng, Yuxia Zhang, Heike Schützle, Sebastian Brenner, Sigrun R Hofmann, Reinhard Berner, Yuanbo Zhao, Bingtai Lu, Xiaoyun Chen, Li Zhang, Suyun Cheng, Stefan Winkler, Kai Lehmberg, Scott W Canna, Peter E Czabotar, Ian P Wicks, Dominic De Nardo, Christian M Hedrich, Huasong Zeng, Seth L Masters
BACKGROUND: Monogenic autoinflammatory disorders are characterised by dysregulation of the innate immune system, for example by gain-of-function mutations in inflammasome forming proteins such as NLRC4. OBJECTIVE: Here we investigate the mechanism by which a novel mutation in the leucine rich repeat (LRR) domain of NLRC4 (c.G1965C, p.W655C) contributes to autoinflammatory disease. METHODS: We studied two unrelated patients with early onset macrophage activation syndrome (MAS) harboring the same de novo mutation in NLRC4...
May 17, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29778217/the-inflammasome-regulation-of-nitric-oxide-and-antimicrobial-host-defence
#2
Rajalaksmy A Ramachandran, Christopher Lupfer, Hasan Zaki
Nitric oxide (NO) is a gaseous signalling molecule that plays diverse physiological functions including antimicrobial host defence. During microbial infection, NO is synthesized by inducible NO synthase (iNOS), which is expressed by host immune cells through the recognition of microbial pattern molecules. Therefore, sensing pathogens or their pattern molecules by pattern recognition receptors (PRRs), which are located at the cell surface, endosomal and phagosomal compartment, or in the cytosol, is key in inducing iNOS and eliciting antimicrobial host defence...
2018: Advances in Microbial Physiology
https://www.readbyqxmd.com/read/29775613/suppression-of-nlrp3-inflammasome-attenuates-stress-induced-depression-like-behavior-in-nlgn3-deficient-mice
#3
Ze-Qun Li, Zhi-Yuan Yan, Bo-Jun Lan, Yi-Qun Dong, Ye Xiong
Depression, regulated by central nervous system (CNS), is a significant inflammatory disorder. Neuroligin3 (NLGN3) has been implicated in brain functions. In the study, a chronic unpredictable mild stress (CUMS) model in wild type (WT) or NLGN3-knockout (KO) mice was established to explore the role of NLGN3 in regulating depression and to reveal the underlying molecular mechanism. The results indicated that NLGN3-knockout markedly reversed the loss of body weight, the reduction of sucrose consumption, the decrease of immobile time in the forced swimming tests (FST) and tail suspension tests (TST) induced by CUMS paradigm...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29774640/regulatory-roles-of-flavonoids-on-inflammasome-activation-during-inflammatory-responses
#4
REVIEW
Young-Su Yi
Inflammation is an innate immune response to noxious stimuli to protect the body from pathogens and dangers. Inflammatory responses consist of two main steps: priming and triggering. In priming, inflammatory cells increase expressions of inflammatory molecules, while in triggering, inflammasomes are activated, resulting in cell death and pro-inflammatory cytokine secretion. Inflammasomes are protein complexes comprising intracellular pattern recognition receptors (PRRs) (e.g. nucleotide-binding oligomerization domain-like receptors (NLRs), absent in melanoma 2 (AIM2), and caspases-4/5/11) and pro-caspase-1 with or without a bipartite adaptor molecule ASC...
May 17, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29774334/a-comparative-study-of-epa-enriched-ethanolamine-plasmalogen-and-epa-enriched-phosphatidylethanolamine-on-a%C3%AE-42-induced-cognitive-deficiency-in-a-rat-model-of-alzheimer-s-disease
#5
Hongxia Che, Qian Li, Tiantian Zhang, Lin Ding, Lingyu Zhang, Haohao Shi, Teruyoshi Yanagita, Changhu Xue, Yaoguang Chang, Yuming Wang
Ethanolamine plasmalogen (pPE), a major phospholipid in neuronal membranes, is specifically reduced in postmortem brains from patients with Alzheimer's disease (AD). The purpose of the present study was to compare the effects of EPA-enriched ethanolamine plasmalogen (EPA-pPE) and EPA-enriched phosphatidylethanolamine (EPA-PE) on cognitive deficiency and illustrate the possible underlying mechanisms. SD rats were divided into four groups including the sham group injected with 0.9% saline and three amyloid-β (Aβ) infusion groups, Aβ42 group, EPA-pPE group and EPA-PE group...
May 18, 2018: Food & Function
https://www.readbyqxmd.com/read/29774028/nlrp3-inflammasome-and-caspase-1-11-pathway-orchestrate-different-outcomes-in-the-host-protection-against-trypanosoma-cruzi-acute-infection
#6
Augusto F Paroli, Patricia V Gonzalez, Cintia Díaz-Luján, Luisina I Onofrio, Alfredo Arocena, Roxana C Cano, Eugenio A Carrera-Silva, Susana Gea
Infection with protozoan parasite Trypanosoma cruzi results in activation of nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs). NLR activation leads to inflammasome formation, the activation of caspase-1, and the subsequent cleavage of IL-1β and IL-18. Considering that inflammasome activation and IL-1β induction by macrophages are key players for an appropriate T cell response, we investigated the relevance of NLR pyrin domain-containing 3 (NLRP3) and caspase-1/11 to elucidate their roles in the induction of different T cell phenotypes and the relationship with parasite load and hepatic inflammation during T...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29772377/impact-of-steroid-hormones-e2-and-p-on-the-nlrp3-asc-casp1-axis-in-primary-mouse-astroglia-and-bv-2-cells-after-in-vitro-hypoxia
#7
Alexander Slowik, Leoni Lammerding, Adib Zendedel, Pardes Habib, Cordian Beyer
Clinical and animal model studies have demonstrated the neuroprotective and anti-inflammatory effects of 17beta-estradiol (E2) and progesterone (P) in different disease models of the central nervous system (CNS) including ischemic stroke. Inflammasomes are involved in the interleukin-1 beta (IL1beta) maturation, in particular, NLRP3, the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and the active caspase-1 (Casp1) form. Recently, we showed that administration of E2 or P selectively regulated these components after experimental ischemic stroke in rats...
May 14, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29771438/methylene-blue-attenuates-renal-ischemia-reperfusion-injury-by-negative-regulation-of-nlrp3-signaling-pathway
#8
J-J Liu, L Lu, F-Q Hu, H Yuan, Q Xu, Y-F Qin, J-H Gong
OBJECTIVE: To investigate the effect of methylene blue (MB) on renal ischemia-reperfusion (IR) injury in mice and its possible relevant mechanisms. MATERIALS AND METHODS: A total of 30 male C57/BL6 mice aged 4 months old were randomly divided into the following three groups: Sham group (n=10), IR group (n=10), and MB group (n=10). Mice in MB group were treated with gavage continuously using methylene blue solution (dosage: 25 mg·kg-1·d-1) until they were 7 months old...
May 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29769797/protective-effects-of-erigeron-breviscapus-hand-mazz-ebhm-extract-in-retinal-neurodegeneration-models
#9
Jingyuan Zhu, Li Chen, Yun Qi, Jing Feng, Li Zhu, Yujing Bai, Huijuan Wu
Purpose: To investigate the neuroprotective effects of scutellarin, an active component of the multifunctional traditional Chinese herb Erigeron breviscapus (vant.) Hand.-Mazz. (EBHM), which has been used as a neuroprotective therapy for cerebrovascular diseases. We performed the experiments using in vitro and in vivo models of retinal neurodegeneration. Methods: In the in vitro experiments, we exposed BV-2 cells to low oxygen levels in an incubator for 24 and 48 h to generate hypoxia models...
2018: Molecular Vision
https://www.readbyqxmd.com/read/29767259/silencing-of-mir%C3%A2-155-suppresses-inflammatory-responses-in-psoriasis-through-inflammasome-nlrp3-regulation
#10
Quan Luo, Jingxin Zeng, Wei Li, Ling Lin, Xin Zhou, Xin Tian, Weiyu Liu, Lidan Zhang, Xibao Zhang
Psoriasis is a dermatosis with the major clinical symptoms of scale, erythema and itching, and it has a long disease course. In addition, it is easily recurrent and refractory, greatly affecting the physical and mental health of patients. In the present study, it was hypothesized that the function of miR‑155 increases psoriasis‑induced inflammation and that its expression may be dependent on inflammasome activation. miR‑155 expression was examined by gene chip array and quantitative polymerase chain reaction analysis...
May 14, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29761921/trans-cinnamic-aldehyde-inhibit-aggregatibacter-actinomycetemcomitans-induced-inflammation-thp-1-derived-macrophages-via-autophagy-activation
#11
Jin Chung, Sumi Kim, Hyun Ah Lee, Mi Hee Park, Seyeon Kim, Yu Ri Song, HeeSam Na
OBJECTIVES: Inflammation is an essential response against bacterial infection as a host defense mechanism, which can lead to tissue damage. Aggregatibacter actinomycetemcomitans (Aa) is major pathogen for aggressive periodontitis characterized by rapid destruction of periodontal tissue surrounding teeth. Trans-cinnamic aldehyde is a key bioactive compound of the cinnamon extracts, which has anti-inflammatory, antioxidant, antipyretic, antimicrobial, and anti-cancer properties. The objective of the present study was to investigate the anti-inflammatory effect of trans-cinnamic aldehyde against Aa infection in human THP-1 derived macrophages and on Aa-induced periodontitis in mice...
May 15, 2018: Journal of Periodontology
https://www.readbyqxmd.com/read/29757557/-effects-of-ginkgo-biloba-extract-combined-with-glucocorticoid-on-olfactory-function-and-inflammatory-cytokines-in-mice-with-allergic-rhinitis
#12
Chan Wu, Yong Xiang Wei, Jayant Marian Pinto, Jun Tian, Xian Dao Yuan, Xiao Jun Zhan
Objective: To determine whether ginkgo biloba extract(GBE)combined with dexamethasone(DEX)plays a role in the treatment of allergic rhinitis-related olfactory dysfunction using an animal model. Method: Six week old BALB/C mice were sensitized and challenged with ovalbumin.30 sensitized mice were divided into three groups:Group 1 was given high-dose GBE and DEX(n=10);Group 2 was given low dose GBE and DEX(n=10);Group 3 was given DEX alone(n=10).We assessed the histology of the olfactory mucosa and serum IL-4,IFN-γ,and caspase 1...
January 20, 2018: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
https://www.readbyqxmd.com/read/29754454/heparinoid-suppresses-der-p-induced-il-1%C3%AE-production-by-inhibiting-erk-and-p38-mapk-pathways-in-keratinocytes
#13
Ryo Utsunomiya, Xiuju Dai, Masamoto Murakami, Hidenori Okazaki, Teruko Tsuda, Hideki Mori, Ken Shiraishi, Mikiko Tohyama, Koji Sayama
Epidermal keratinocytes initiate skin inflammation by activating immune cells. The skin barrier is disrupted in atopic dermatitis (AD) and epidermal keratinocytes can be exposed to environmental stimuli, such as house dust mite (HDM) allergens. We showed previously that HDM allergens activate the NLRP3 inflammasome of keratinocytes, thereby releasing pro-inflammatory cytokines. Heparinoid is an effective moisturizer for atopic dry skin. However, a recent report showed that heparinoid treatment can improve inflammation of lichen planus...
May 13, 2018: Experimental Dermatology
https://www.readbyqxmd.com/read/29752727/clinical-periodontal-status-and-inflammatory-cytokines-in-primary-sjogren-syndrome-and-rheumatoid-artritis
#14
Özgün Özçaka, Esin Alpöz, Ayşe Nalbantsoy, Gonca Karabulut, Yasemin Kabasakal
BACKGROUND: The aim of the present study is to compare the clinical periodontal findings as well as gingival crevicular fluid (GCF) and plasma levels of tumour necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), Interferon gamma (IFN-γ) and Caspase-1 in primary Sjögren's Syndrome (pSS) and Rheumatoid Arthritis (RA) subjects. METHODS: In the present case control study plasma and GCF samples were collected, full-mouth recordings comprising plaque index (PI), bleeding on probing (BOP) and probing depth (PD) were performed in 44 subjects with pSS, 39 subjects with RA and 30 systemically healthy subjects...
May 11, 2018: Journal of Periodontology
https://www.readbyqxmd.com/read/29743981/induction-of-nlrp3-inflammasome-activation-by-heme-in-human-endothelial-cells
#15
Judit Erdei, Andrea Tóth, Enikő Balogh, Benard Bogonko Nyakundi, Emese Bányai, Bernhard Ryffel, György Paragh, Mario D Cordero, Viktória Jeney
Hemolytic or hemorrhagic episodes are often associated with inflammation even when infectious agents are absent suggesting that red blood cells (RBCs) release damage-associated molecular patterns (DAMPs). DAMPs activate immune and nonimmune cells through pattern recognition receptors. Heme, released from RBCs, is a DAMP and induces IL-1 β production through the activation of the nucleotide-binding domain and leucine-rich repeat-containing family and pyrin domain containing 3 (NLRP3) in macrophages; however, other cellular targets of heme-mediated inflammasome activation were not investigated...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29743866/dexmedetomidine-inhibits-inflammation-in-microglia-cells-under-stimulation-of-lps-and-atp-by-c-fos-nlrp3-caspase-1-cascades
#16
Hu Li, Xueping Zhang, Mingfu Chen, Jianyan Chen, Tao Gao, Shanglong Yao
NOD-like receptor 3 (NLRP3) plays critical roles in the initiation of inflammasome-mediated inflammation in microglia, thus becomes an important therapeutic target of Alzheimer's disease (AD). Dexmedetomidine (Dex), a new type of clinical anesthetic agent, shows anti-inflammatory properties and inhibits postoperative cognitive dysfunction in AD patients. The present study was aimed to investigate effect of Dex on NLRP3 activity in activated microglia and reveal the underlying mechanisms. The human microglia clone 3 (HMC3) cells were exposed to 100 ng/ml LPS and 5 mM ATP, in the presence and absence of doses of Dex...
2018: EXCLI Journal
https://www.readbyqxmd.com/read/29742060/renal-involvement-in-autoinflammatory-diseases-and-inflammasome-mediated-chronic-kidney-damage
#17
REVIEW
Roberto Scarpioni, Laura Obici
Unprovoked activation of innate immune pathways and increased secretion of interleukin (IL)-1β and IL-18 are responsible for the protean clinical manifestations and the marked inflammatory response that characterise most hereditary autoinflammatory disorders. The kidney is a major target organ of this inflammatory process. The deposition of the acute-phase reactant serum amyloid A (SAA) as amyloid causes progressive glomerular and vascular damage and leads to organ failure. In this review we focus on the potential impact of hereditary autoinflammatory diseases on renal function, provide red flags that may guide the clinical suspicion of amyloid kidney damage and discuss the relevance of close renal monitoring for early diagnosis and prompt treatment...
January 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29740850/therapeutic-effects-of-artemisia-scoparia-waldst-et-kitaib-in-a-murine-model-of-atopic-dermatitis
#18
K J Ryu, M S Yoou, Y Seo, K W Yoon, H M Kim, H J Jeong
BACKGROUND: Artemisia scoparia Waldst. et Kitaib (AS) (Oriental wormwood, known as Bissuk in Korea) is a plant used in cosmetic and pharmaceutical treatments. However, the effect of AS on atopic dermatitis (AD) has not been described. AIM: To examine the inhibitory effect of AS on AD using a murine model. METHODS: We applied either AS, the butanol-extracted fraction of AS (Bu-OH) or 3,5-dicaffeoyl-epi-quinic acid (DEQA, a major component of Bu-OH) topically for 3 weeks to 2,4-dinitrofluorobenzene (DNFB)-induced skin lesions in BALB/c mice...
May 8, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29739853/mycobacterium-tuberculosis-ppe60-antigen-drives-th1-th17-responses-via-toll-like-receptor-2-dependent-maturation-of-dendritic-cells
#19
Haibo Su, Zhen Zhang, Zijian Liu, Baozhou Peng, Cong Kong, Honghai Wang, Zhi Zhang, Ying Xu
Targeting of Mycobacterium tuberculosis (MTB) PE/PPE antigens that induce type 1 helper T cell (Th1) and Th17 responses represents a crucial strategy for the development of tuberculosis (TB) vaccines. However, only few PE/PPE antigens induce these responses. Here, we sought to determine how the cell wall-associated antigen PPE60 (Rv3478) activates dendritic cell (DC) maturation and T-cell differentiation. We observed that PPE60 induces DC maturation by augmenting the protein expression of cluster of differentiation 80 (CD80) and CD86, and major histocompatibility complex (MHC) class I and MHC class II on the cell surface...
May 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29738879/regulation-of-signaling-by-cooperative-assembly-formation-in-mammalian-innate-immunity-signalosomes-by-molecular-mimics
#20
REVIEW
Jeffrey D Nanson, Habibur Rahaman, Thomas Ve, Bostjan Kobe
Innate immunity pathways constitute the first line of defense against infections and cellular damage. An emerging concept in these pathways is that signaling involves the formation of finite (e.g. rings in NLRs) or open-ended higher-order assemblies (e.g. filamentous assemblies by members of the death-fold family and TIR domains). This signaling by cooperative assembly formation (SCAF) mechanism allows rapid and strongly amplified responses to minute amounts of stimulus. While the characterization of the molecular mechanisms of SCAF has seen rapid progress, little is known about its regulation...
May 5, 2018: Seminars in Cell & Developmental Biology
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