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https://www.readbyqxmd.com/read/28633109/endothelial-nlrp3-inflammasome-activation-and-arterial-neointima-formation-associated-with-acid-sphingomyelinase-during-hypercholesterolemia
#1
Saisudha Koka, Min Xia, Yang Chen, Owais M Bhat, Xinxu Yuan, Krishna M Boini, Pin-Lan Li
The NLRP3 inflammasome has been reported to be activated by atherogenic factors, whereby endothelial injury and consequent atherosclerotic lesions are triggered in the arterial wall. However, the mechanisms activating and regulating NLRP3 inflammasomes remain poorly understood. The present study tested whether acid sphingomyelinase (ASM) and ceramide associated membrane raft (MR) signaling platforms contribute to the activation of NLRP3 inflammasomes and atherosclerotic lesions during hypercholesterolemia. We found that 7-ketocholesterol (7-Keto) or cholesterol crystal (ChC) markedly increased the formation and activation of NLRP3 inflammasomes in mouse carotid arterial endothelial cells (CAECs), as shown by increased colocalization of NLRP3 with ASC or caspase-1, enhanced caspase-1 activity and elevated IL-1β levels, which were markedly attenuated by mouse Asm siRNA, ASM inhibitor- amitriptyline, and deletion of mouse Asm gene...
June 15, 2017: Redox Biology
https://www.readbyqxmd.com/read/28631886/nlrp3-expression-and-urinary-hsp72-in-relation-to-biomarkers-of-inflammation-and-oxidative-stress-in-diabetic-nephropathy-patients
#2
Hemat El-Sayed El-Horany, Rania Nagi Abd-Ellatif, Mona Watany, Yasser M Hafez, Hanaa Ibrahim Okda
Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease. Nod-like receptors nucleotide-binding domain and leucine-rich repeat pyrin-3 domain (NLRP3) inflammasome displays a considerable role in the chronic inflammatory state observed in diabetic patients. Urinary heat shock protein 72 (uHSP72) is a sensitive and specific biomarker for the early detection of acute kidney injury. The aim of this study was to evaluate NLRP3 relative gene expression, its correlation with inflammatory and oxidative stress markers, and to assess the value of uHSP72 in the early detection of DN in type 2 diabetic patients with different degrees of DN...
June 20, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28631084/nlrp3-inflammasome-in-inflammatory-bowel-disease-friend-or-foe
#3
EDITORIAL
Ling Liu, Xuhang Li
No abstract text is available yet for this article.
June 19, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28629999/trimethylamine-n-oxide-prime-nlrp3-inflammasome-via-inhibiting-atg16l1-induced-autophagy-in-colonic-epithelial-cells
#4
Chaochi Yue, Xiangdong Yang, Jun Li, Xiaochao Chen, Xiangdong Zhao, Ye Chen, Yong Wen
Recently, the intricate relationship between Trimethylamine N-oxide (TMAO) and inflammatory bowel disease (IBD) is of growing interest. The NLRP3 inflammasome plays crucial roles in gut homeostasis and determining the severity of inflammation in IBD, however, the precise roles of the NLRP3 inflammasome in IBD are still debated. ATG16L1 mediates the cellular degradative process of autophagy and is considered a critical regulator of inflammation based on its genetic association with IBD. Whether TMAO prime NLRP3 inflammasome via ATG16L1-induced autophagy remains unclear...
June 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28628921/activation-of-cox-2-mpges-1-pge2-cascade-via-nlrp3-inflammasome-contributes-to-albumin-induced-proximal-tubule-cell-injury
#5
Yibo Zhuang, Fei Zhao, Jing Liang, Xu Deng, Yue Zhang, Guixia Ding, Aihua Zhang, Zhanjun Jia, Songming Huang
BACKGROUND/AIMS: The activation of NOD-like receptor family, pyrin domain containing3 (NLRP3) inflammasome has been shown to be positively correlated with the severity of proteinuria in chronic kidney disease (CKD) patients. Prostaglandin E2 (PGE2), an important inflammatory mediator, is also involved in various kidney injuries. The aim of the present study was to investigate the involvement of NLRP3 inflammasome and PGE2 synthetic pathway in albumin-induced renal tubular injury. METHODS: Murine proximal tubular cells (mPTCs) were treated with albumin to induce cell injury...
June 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28623945/mir-155-is-overexpressed-in-systemic-sclerosis-fibroblasts-and-is-required-for-nlrp3-inflammasome-mediated-collagen-synthesis-during-fibrosis
#6
Carol M Artlett, Sihem Sassi-Gaha, Jennifer L Hope, Carol A Feghali-Bostwick, Peter D Katsikis
BACKGROUND: Despite the important role that microRNAs (miRNAs) play in immunity and inflammation, their involvement in systemic sclerosis (SSc) remains poorly characterized. miRNA-155 (miR-155) plays a role in pulmonary fibrosis and its expression can be induced with interleukin (IL)-1β. SSc fibroblasts have activated inflammasomes that are integrally involved in mediating the myofibroblast phenotype. In light of this, we investigated whether miR-155 played a role in SSc and if its expression was dependent on inflammasome activation...
June 17, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28623127/the-inhibition-of-nlrp3-signaling-attenuates-liver-injury-in-an-%C3%AE-galactosylceramide-induced-hepatitis-model
#7
Ayumu Kanbe, Hiroyasu Ito, Yukari Omori, Akira Hara, Mitsuru Seishima
Inflammasomes are involved in innate immune responses. Several NOD-Like receptors (NLRs) participate in the formation of inflammasomes. NACHT, LRR and PYD domains-containing protein 3 (NALP3) belongs to the NLR family and recognizes adenosine triphosphate (ATP), crystals, and Reactive Oxygen Species (ROS). This study examined the effect of inflammasomes on alpha-galactosylceramide (GalCer)-induced liver injury using NALP3-knockout (KO) mice. GalCer administration induced inflammasome activation and IL-1β-maturation...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28619106/bone-mesenchymal-stem-cells-ameliorate-ischemia-reperfusion-induced-damage-in-renal-epithelial-cells-via-microrna-223
#8
Xiaopeng Yuan, Xiaoping Wang, Chuanbao Chen, Jian Zhou, Ming Han
BACKGROUND: Recent studies have indicated that microRNA-223 (miR-223) plays a role in the tissue-protective effect of mesenchymal stem cells (MSCs). NLR family-pyrin domain containing 3 (NLRP3) was reported to affect a renal ischemia/reperfusion (I/R) injury by exerting a direct effect on the renal tubular epithelium. Therefore, we investigated how miR-223 and NLRP3 might function in kidneys exposed to conditions of ischemia and subsequent reperfusion. METHODS: Hypoxia/reoxygenation (H/R) murine renal tubular epithelial cells (RTECs) were cocultured with either MSCs or hypoxia-pretreated MSCs (htMSCs), after which the RTECs were examined for their viability and evidence of apoptosis...
June 15, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28618410/deletion-of-the-inflammasome-sensor-aim2-mitigates-a%C3%AE-deposition-and-microglial-activation-but-increases-inflammatory-cytokine-expression-in-an-alzheimer-disease-mouse-model
#9
Pei-Jung Wu, Yun-Fen Hung, Hsin-Yu Liu, Yi-Ping Hsueh
OBJECTIVE: Inflammation is clearly associated with Alzheimer disease (AD). Knockout of Nlrp3, a gene encoding an inflammasome sensor, has been shown to ameliorate AD pathology in a mouse model. Because AIM2 is the most dominant inflammasome sensor expressed in mouse brains, here we investigate whether Aim2 deletion also influences the phenotype of a 5XFAD AD mouse model. METHODS: Quantitative RT-PCR, immunostaining, immunoblotting, and behavioral analyses were applied to compare wild-type, Aim2-/-, 5XFAD, and Aim2-/-;5XFAD mice...
June 16, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/28615649/andrographolide-ameliorates-inflammation-and-fibrogenesis-and-attenuates-inflammasome-activation-in-experimental-non-alcoholic-steatohepatitis
#10
Daniel Cabrera, Alexander Wree, Davide Povero, Nancy Solís, Alejandra Hernandez, Margarita Pizarro, Han Moshage, Javiera Torres, Ariel E Feldstein, Claudio Cabello-Verrugio, Enrique Brandan, Francisco Barrera, Juan Pablo Arab, Marco Arrese
Therapy for nonalcoholic steatohepatitis (NASH) is limited. Andrographolide (ANDRO), a botanical compound, has a potent anti-inflammatory activity due to its ability to inhibit NF-κB. ANDRO has been also shown to inhibit the NLRP3 inflammasome, a relevant pathway in NASH. Our aim was to evaluate the effects of ANDRO in NASH and its influence on inflammasome activation in this setting. Thus, mice were fed a choline-deficient-amino-acid-defined (CDAA) diet with/without concomitant ANDRO administration (1 mg/kg, 3-times/week)...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615462/posttranslational-modification-as-a-critical-determinant-of-cytoplasmic-innate-immune-recognition
#11
REVIEW
Paul J Baker, Dominic De Nardo, Fiona Moghaddas, Le Son Tran, Annabell Bachem, Tan Nguyen, Thomas Hayman, Hazel Tye, James E Vince, Sammy Bedoui, Richard L Ferrero, Seth L Masters
Cell surface innate immune receptors can directly detect a variety of extracellular pathogens to which cytoplasmic innate immune sensors are rarely exposed. Instead, within the cytoplasm, the environment is rife with cellular machinery and signaling pathways that are indirectly perturbed by pathogenic microbes to activate intracellular sensors, such as pyrin, NLRP1, NLRP3, or NLRC4. Therefore, subtle changes in key intracellular processes such as phosphorylation, ubiquitination, and other pathways leading to posttranslational protein modification are key determinants of innate immune recognition in the cytoplasm...
July 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28614830/expression-of-tlr2-nod1-and-nod2-and-the-nlrp3-inflammasome-in-renal-tubular-epithelial-cells-of-male-versus-female-mice
#12
Sean E DeWolf, Alana A Shigeoka, Andrew Scheinok, Sashi G Kasimsetty, Alexander K Welch, Dianne B McKay
BACKGROUND: Gender-biased outcomes are associated with acute kidney injury (AKI) and human and animal studies have shown that females are preferentially protected from renal ischemia. However, the reason for this is not known. One clue might lie with pattern recognition receptors (PRRs), which are triggers of ischemic injury when ligated by molecules in the ischemic milieu. Several PRR families are expressed by renal tubular epithelial cells (RTEs) and incite cell death signaling and production of pro-inflammatory molecules...
June 15, 2017: Nephron
https://www.readbyqxmd.com/read/28612844/nlrp3-inflammasome-pathway-has-a-critical-role-in-the-host-immunity-against-clinically-relevant-acinetobacter-baumannii-pulmonary-infection
#13
N Dikshit, S D Kale, H J Khameneh, V Balamuralidhar, C Y Tang, P Kumar, T P Lim, T T Tan, A L Kwa, A Mortellaro, B Sukumaran
The opportunistic Gram-negative bacterium Acinetobacter baumannii (AB) is a leading cause of life-threatening nosocomial pneumonia. Outbreaks of multidrug resistant (MDR)-AB belonging to international clones (ICs) I and II with limited treatment options are major global health threats. However, the pathogenesis mechanisms of various AB clonal groups are understudied. Although inflammation-associated interleukin-1β (IL-1β) levels and IL-1 receptor antagonist polymorphisms were previously implicated in MDR-AB-related pneumonia in patients, whether inflammasomes has any role in the host defense and/or pathogenesis of clinically relevant A...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28612258/downregulated-glia-interplay-and-increased-mirna-155-as-promising-markers-to-track-als-at-an%C3%A2-early-stage
#14
Carolina Cunha, Catarina Santos, Cátia Gomes, Adelaide Fernandes, Alexandra Marçal Correia, Ana Maria Sebastião, Ana Rita Vaz, Dora Brites
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown cause. Absence of specific targets and biomarkers compromise the development of new therapeutic strategies and of innovative tools to stratify patients and assess their responses to treatment. Here, we investigate changes in neuroprotective-neuroinflammatory actions in the spinal cord of SOD1 (G93A) mice, at presymptomatic and symptomatic stages to identify stage-specific biomarkers and potential targets. Results showed that in the presymptomatic stage, there are alterations in both astrocytes and microglia, which comprise decreased expression of GFAP and S100B and upregulation of GLT-1, as well as reduced expression of CD11b, M2-phenotype markers, and a set of inflammatory mediators...
June 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28610608/isoliquiritigenin-alleviates-early-brain-injury-after-experimental-intracerebral-hemorrhage-via-suppressing-ros-and-or-nf-%C3%AE%C2%BAb-mediated-nlrp3-inflammasome-activation-by-promoting-nrf2-antioxidant-pathway
#15
Jun Zeng, Yizhao Chen, Rui Ding, Liang Feng, Zhenghao Fu, Shuo Yang, Xinqing Deng, Zhichong Xie, Shizhong Zheng
BACKGROUND: Intracerebral hemorrhage (ICH) induces potently oxidative stress responses and inflammatory processes. Isoliquiritigenin (ILG) is a flavonoid with a chalcone structure and can activate nuclear factor erythroid-2 related factor 2 (Nrf2)-mediated antioxidant system, negatively regulate nuclear factor-κB (NF-κB) and nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathways, but its role and potential molecular mechanisms in the pathology following ICH remain unclear...
June 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28606793/mir-20b-inhibits-mycobacterium-tuberculosis-induced-inflammation-in-the-lung-of-mice-through-targeting-nlrp3
#16
Jun Lou, Yongli Wang, Zhimin Zhang, Weiqiang Qiu
Tuberculosis (TB) is one of immune-related disorders. Although dysregulation of miRNAs has been implicated in innate and adaptive immune response, the specific effect of miR-20b on TB has not been documented. In this study, downregulation of miR-20b and upregulation of NLRP3 were observed in macrophages of TB patients, increased levels of inflammatory factors secretion were observed in serum of TB patients. Next, we established a TB mice model by using M. tuberculosis infection and intravenous injection of miR-20b mimic...
June 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28604600/transcriptional-responses-in-the-murine-spleen-after-toxoplasma-gondii-infection-inflammasome-and-mucus-associated-genes
#17
Eva B Znalesniak, Ting Fu, Franz Salm, Ulrike Händel, Werner Hoffmann
The spleen plays an important role in coordinating both adaptive and innate immune responses. Here, the transcriptional response to T. gondii infection in the murine spleen was characterized concerning inflammasome sensors (two different models: seven days after oral or four weeks after intraperitoneal infection). Additionally, Tff1(KO) and Tff3(KO) mice were investigated because TFF genes are often upregulated during inflammation. The expression of the pattern-recognition receptors Nlrp3, Nlrp12, and Nlrp1a was significantly increased after infection...
June 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28603491/nosh-nbp-a-novel-nitric-oxide-and-hydrogen-sulfide-releasing-hybrid-attenuates-ischemic-stroke-induced-neuroinflammatory-injury-by-modulating-microglia-polarization
#18
Jing Ji, Pengjun Xiang, Tingting Li, Li Lan, Xiaole Xu, Guo Lu, Hui Ji, Yihua Zhang, Yunman Li
NOSH-NBP, a novel nitric oxide (NO) and hydrogen sulfide (H2S)-releasing hybrid, protects brain from ischemic stroke. This study mainly aimed to investigate the therapeutic effect of NOSH-NBP on ischemic stroke and the underlying mechanisms. In vivo, transient middle cerebral artery occlusion (tMCAO) was performed in C57BL/6 mice, with NO-NBP and H2S-NBP as controls. NO and H2S scavengers, carboxy-PTIO and BSS, respectively, were used to quench NO and H2S of NOSH-NBP. In vitro, BV2 microglia/BMDM were induced to the M1/2 phenotype, and conditioned medium (CM) experiments in BV2 microglia, neurons and b...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28603274/lupus-nephritis-role-of-nlrp3-inflammasomes-in-podocyte-injury
#19
Ellen F Carney
No abstract text is available yet for this article.
June 12, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28600543/innate-and-adaptive-immunity-are-progressively-activated-in-parallel-with-renal-injury-in-the-5-6-renal-ablation-model
#20
Camilla Fanelli, Simone C A Arias, Flavia G Machado, Jessica K Okuma, Denise M A C Malheiros, Hatylas Azevedo, Carlos A Moreira-Filho, Niels O S Camara, Clarice K Fujihara, Roberto Zatz
The mechanisms triggering renal inflammation in chronic kidney disease (CKD) are unclear. We performed a detailed analysis of the time course of innate and adaptive immunity activation in the 5/6 renal ablation (Nx) model. Munich-Wistar rats undergoing Nx were studied 15, 60 and 120 days after ablation. Hypertension, albuminuria, creatinine retention, interstitial expansion and infiltration by macrophages and T-lymphocytes were already evident 15 days after Nx. PCR-array was used to screen for altered gene expression, whereas gene and protein expressions of TLR4, CASP1, IL-1β and NLRP3 were individually assessed...
June 9, 2017: Scientific Reports
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