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NLRP3 inflammasome

Lena Walenta, Nina Schmid, J U Schwarzer, Frank-Michael Köhn, Henryk Urbanski, Ruediger Behr, Leena Strauss, Matti Poutanen, Artur Mayerhofer
NLRP3 is part of the NLRP3 inflammasome and a global sensor of cellular damage. It was recently discovered in rodent Sertoli cells. We investigated NLRP3 in mouse, human and non-human primate (marmoset and rhesus macaque) testes, employing immunohistochemistry. Sertoli cells of all species expressed NLRP3, and the expression preceded puberty. In addition, peritubular cells of the adult human testes expressed NLRP3. NLRP3 and associated genes (ASC, CASP1, IL1B) were also found in isolated human testicular peritubular cells (HTPCs) and the mouse Sertoli cell line TM4...
June 15, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
Karam Kim, Hye Jeong Kim, Bert Binas, Jin Hyun Kang, Il Yup Chung
Danger-associated molecular patterns (DAMPs) play a proinflammatory role in the pathogenesis of airway obstructive diseases such as severe asthma and chronic obstructive pulmonary disease. The NLRP3 inflammasome is a cytosolic multiprotein platform that activates the caspase-1 pathway in response to inflammatory stimuli such as DAMPs. ATP and S100 proteins are newly identified DAMPs that accumulate in inflamed airways. We previously demonstrated that S100A8, S100A9, and S100A12 induce production and secretion of MUC5AC, a major mucin in the conducting airway mucosa...
June 12, 2018: Biochemical and Biophysical Research Communications
S Ran, M Chu, S Gu, J Wang, J Liang
AIM: To investigate the ability of E. faecalis to cause apoptosis and pyroptosis of human osteoblastic MG63 cells and whether the inflammasome is involved in this process. METHODOLOGY: MG63 cells were infected with E. faecalis at a multiplicity of infection (MOI) of 10, 100, 500, and 1000 for 6 and 12 h. The cell proliferation was determined with the Cell Counting Kit-8. Apoptosis and pyroptosis after E. faecalis infection was evaluated by flow cytometry and a lactate dehydrogenase (LDH) cytotoxicity assay kit...
June 14, 2018: International Endodontic Journal
Wenzhe Yu, Mengru Tao, Yueliang Zhao, Xiaoqian Hu, Mingfu Wang
Advanced glycation end products (AGEs) could interact with the receptor for AGE (RAGE) as a sterile danger signal to induce inflammation. 4′-methoxyresveratrol (4′MR), a polyphenol derived from Dipterocarpaceae, has not been studied for its anti-inflammation effects. In the present study, we sought to explore the protective role of 4′MR in AGEs-induced inflammatory model using RAW264.7 macrophages. 4′MR significantly inhibited gene expression of pro-inflammatory cytokines and chemokines, such as interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), as well as two typical pro-inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2)...
June 14, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Francis J Herman, Giulio Maria Pasinetti
The production of inflammatory proteins by the innate immune system is a tightly orchestrated procedure that allows the body to efficiently respond to exogenous and endogenous threats. Recently, accumulating evidence has indicated that disturbances in the inflammatory response system not only provoke autoimmune disorders, but also can have deleterious effects on neuronal function and mental health. As inflammation in the brain is primarily mediated by microglia, there has been an expanding focus on the mechanisms through which these cells initiate and propagate neuroinflammation...
June 11, 2018: Brain, Behavior, and Immunity
Yingchun Qiao, Xixi Tian, Li Men, Shengyu Li, Yufeng Chen, Meiting Xue, Yahui Hu, Pengfei Zhou, Guangfeng Long, Yue Shi, Ruiqing Liu, Yunde Liu, Zhi Qi, Yujie Cui, Yanna Shen
Diabetic nephropathy (DN) is a serious complication of diabetes and can cause an increased mortality risk. It was previously reported that NLR family pyrin domain containing 3 (NLRP3) inflammasome is involved in the pathogenesis of diabetes. However, the underlying mechanism is not clearly understood. In the present study, the effects of spleen tyrosine kinase (Syk) and c‑Jun N‑terminal kinase (JNK) on the NLRP3 inflammasome were examined in vivo and in vitro. Sprague‑Dawley rats were injected intraperitoneally with streptozotocin (65 mg/kg) to induce diabetes...
June 14, 2018: Molecular Medicine Reports
Yichen Xiao, Wenna Xu, Wenru Su
Allergic diseases, such as asthma, rhinitis, dermatitis, conjunctivitis, and anaphylaxis, have recently become a global public health concern. According to previous studies, the NLRP3 inflammasome is a multi-protein complex known to be associated with many inflammatory conditions. In response to allergens or allergen/damage-associated molecular signals, NLRP3 changes its conformation to allow the assembly of the NLRP3 inflammasome complex and activates caspase-1, which is an evolutionarily conserved enzyme that proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines IL-1β and IL-18...
June 13, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Xiao-Juan Zhao, Yan-Zi Yang, Yan-Jing Zheng, Shan-Chun Wang, Hong-Mei Gu, Ying Pan, Shui-Juan Wang, Hong-Jiang Xu, Ling-Dong Kong
The data presented herein are related to the research article entitled "Magnesium isoglycyrrhizinate blocks fructose-induced hepatic NF-κB/NLRP3 inflammasome activation and lipid metabolism disorder" (Zhao et al., 2017) [1]. This article describes the effects of magnesium isoglycyrrhizinate on 24-h food or water intake in fructose-fed rats at 15-week. In addition, this article expands the effect of magnesium isoglycyrrhizinate on the animal body weight change during 1-17 week. The field dataset is made publicly available to enable critical or extended analyzes...
June 2018: Data in Brief
Yali Chen, Mengmei Yin, Xuejin Cao, Gang Hu, Ming Xiao
Both hypercholesterolemia and aging are related to cognitive decline or Alzheimer's disease. However, their interactive influence on the neurodegenerative progress remains unclear. To address this issue, 6-month-old and 16-month-old female mice were fed a 3% cholesterol diet for 8 weeks, followed by hippocampus-related functional, pathological, biochemical and molecular analyses. The high cholesterol diet did not exacerbate age-dependent cognitive decline and hippocampal neuronal death, and even greatly mitigated decreases of synaptophysin and growth associated protein 43 expression in the hippocampus of aged mice...
June 2018: Aging and Disease
Xuyun Gu, Chen Wei, Xishan Zhu, Feiping Lu, Bo Sheng, Xuefeng Zang
Sepsis with severe systemic inflammation remains a great challenge for the intensive care unit in clinics. Although biomarkers have been identified to diagnose, monitor and predict these syndromes, novel therapeutic approaches are required for the amelioration of symptoms of sepsis and septic shock. The present study demonstrated that interleukin (IL)-31 was able reduce the mortality rate of lipopolysaccharide (LPS)-induced sepsis with the reduction of inflammatory cytokines in the sera. IL-31 also inhibited IL-1β production in the peritoneal lavage fluid in LPS-induced or cecal ligation and puncture-induced sepsis...
July 2018: Experimental and Therapeutic Medicine
Finosh G Thankam, Zachary K Roesch, Matthew F Dilisio, Mohamed M Radwan, Anuradha Kovilam, R Michael Gross, Devendra K Agrawal
Inflammation and extracellular matrix (ECM) disorganization following the rotator cuff tendon injuries (RCTI) delay the repair and healing process and the molecular mechanisms underlying RCTI pathology are largely unknown. Here, we examined the role of HMGB1 and NLRP3 inflammasome pathway in the inflammation and ECM disorganization in RCTI. This hypothesis was tested in a tenotomy-RCTI rat model by transecting the RC tendon from the humerus. H&E and pentachrome staining revealed significant changes in the morphology, architecture and ECM organization in RC tendon tissues following RCTI when compared with contralateral control...
June 11, 2018: Scientific Reports
Jie Yang, Zhonghua Liu, Chuanping Wang, Rui Yang, Joseph K Rathkey, Otis W Pinkard, Wuxian Shi, Yinghua Chen, George R Dubyak, Derek W Abbott, Tsan Sam Xiao
The inflammasomes are signaling platforms that promote the activation of inflammatory caspases such as caspases-1, -4, -5, and -11. Recent studies identified gasdermin D (GSDMD) as an effector for pyroptosis downstream of the inflammasome signaling pathways. Cleavage of GSDMD by inflammatory caspases allows its N-terminal domain to associate with membrane lipids and form pores that induce pyroptotic cell death. Despite the important role of GSDMD in pyroptosis, the molecular mechanisms of GSDMD recognition and cleavage by inflammatory caspases that trigger pyroptosis are poorly understood...
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jinfeng Li, Bing Wang, Guangjie Zhou, Xiujuan Yan, Yuan Zhang
BACKGROUND: Tetrahydroxy stilbene glucoside (TSG) is an active ingredient of Heshouwu and is an antioxidant. The underlying mechanisms of the renoprotective effect of TSG in diabetic nephropathy have not been previously reported. In this study, we investigated the mechanisms of TSG in preventing podocytes injury in high glucose (HG) condition. METHODS: Cultured mouse podocytes (MPC5) were incubated in HG (30mmol/L) plus various concentration of TSG (0.1, 1 and 10μM) for 48 hours...
June 2018: American Journal of the Medical Sciences
J Magarian Blander, Gaetan Barbet
Live attenuated vaccines elicit stronger protective immunity than dead vaccines. Distinct PAMPs designated as vita-PAMPs signify microbial viability to innate immune cells. Two vita-PAMPs have been characterized: cyclic-di-adenosine-monophosphate (c-di-AMP) and prokaryotic messenger RNA (mRNA). c-di-AMP produced by live Gram-positive bacteria elicits augmented production of STING-dependent type-I interferon, whereas prokaryotic mRNA from live bacteria is detected by TLR8 enabling discrimination of live from dead bacteria...
June 8, 2018: Current Opinion in Pharmacology
Jing Huang, Tao Wang, Daorui Yu, Xingyue Fang, Haofei Fan, Qiang Liu, Guohui Yi, Xinan Yi, Qibin Liu
We investigated the therapeutic effects of l-homocarnosine against inflammation in a rat model of cerebral ischemia-reperfusion injury. Rats were grouped into control, middle cerebral artery occlusion (MCAO), 0.5 mM l-homocarnosine + MCAO, and 1 mM l-homocarnosine + MCAO treatment groups. Superoxide dismutase (SOD), glutathione peroxidase (Gpx), catalase, lipid peroxidation, and reduced glutathione (GSH) levels were measured. Neurological scores were assessed, and histopathology, scanning electron microscopy (SEM), and fluorescence microscopy analyses were conducted...
June 8, 2018: International Journal of Biological Macromolecules
Fateme Shamekhi Amiri
Subcellular organelles consist of smaller substructures called supramolecular assemblies and these in turn consist of macromolecules. Various subcellular organelles have critical functions that consist of genetic disorders of organelle biogenesis and several metabolic disturbances that occur during non-genetic diseases e.g. infection, intoxication and drug treatments. Mitochondrial damage can cause renal dysfunction as ischemic acute renal injury, chronic kidney disease progression. Moreover, mitochondrial dysfunction is an early event in aldosterone-induced podocyte injury and cardiovascular disease due to oxidative stress in chronic kidney disease...
June 7, 2018: Néphrologie & Thérapeutique
Li Yang, Tatsuki Mizuochi, Pranavkumar Shivakumar, Reena Mourya, Zhenhua Luo, Sridevi Gutta, Jorge A Bezerra
BACKGROUND & AIMS: Biliary atresia (BA) results from a neonatal inflammatory and fibrosing obstruction of bile ducts of unknown etiology. Although the innate immune system has been linked to virus-induced mechanism of disease, the role of the inflammasome-mediated epithelial injury remains largely undefined. Here, we hypothesized that disruption of the inflammasome suppresses the neonatal proinflammatory response and prevents experimental BA. METHODS: We determined the expression of key inflammasome-related genes in livers from infants at diagnosis of BA and in extrahepatic bile ducts (EHBDs) of neonatal mice after infection with rotavirus (RRV) immediately after birth...
June 7, 2018: Journal of Hepatology
Linfang Chen, Liujun Xue, Jinlong Zheng, Xiangyang Tian, Yingdong Zhang, Qiang Tong
Recent studies have indicated that peroxisome proliferator-activated receptor β/δ (PPARß/δ) agonists exert neuroprotective effects in the model of Parkinson's disease (PD). Furthermore, PPARß/δ agonists have been shown to have potential anti-inflammatory activity, but the underlying mechanisms remain obscure. Emerging evidence indicates that the nucleotide-binding domain and leucine-rich-repeat-protein 3 (NLRP3) inflammasome-mediated neuroinflammation plays a crucial role in the pathogenesis of PD. In the present study we investigate whether PPARß/δ agonists alleviate NLRP3-mediated neuroinflammation in the 1- methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model of PD...
June 7, 2018: Behavioural Brain Research
Shalini Swaroop, Anita Mahadevan, Susarla Krishna Shankar, Yogita K Adlakha, Anirban Basu
BACKGROUND: Interleukin-1β (IL-1β) is one of the most important cytokine secreted by activated microglia as it orchestrates the vicious cycle of inflammation by inducing the expression of various other pro-inflammatory cytokines along with its own production. Microglia-mediated IL-1β production is a tightly regulated mechanism which involves the activation of nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome pathway. Our previous study suggests the critical role of heat shock protein 60 (HSP60) in IL-1β-induced inflammation in microglia through TLR4-p38 MAPK axis...
June 9, 2018: Journal of Neuroinflammation
Jingwei Shang, Toru Yamashita, Yun Zhai, Yumiko Nakano, Ryuta Morihara, Xianghong Li, Feng Tian, Xia Liu, Yong Huang, Xiaowen Shi, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe
Cerebral neuroinflammation defines a novel pathway for progressing Alzheimer's disease (AD) pathology. We investigated immunohistological changes of neuroinflammation with nucleotide-binding domain and leucine-rich repeat (NLR)-protein 3 (NLRP3), activated caspase-1 and interleukin-1 beta (IL-1β) in a novel AD (APP23) mice with chronic cerebral hypoperfusion (CCH) model from 4 months (M) of age, moreover, examined protective effect of galantamine. CCH strongly enhanced NLRP3, activated caspase-1 and IL-1β expressions in hippocampus and thalamus at age 12 M of AD mice...
June 6, 2018: Neuroscience Research
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