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Enrico Gugliandolo, Roberta Fusco, Giovanna Ginestra, Ramona D'amico, Carlo Bisignano, Giuseppina Mandalari, Salvatore Cuzzocrea, Rosanna Di Paola
BACKGROUND: Colonization with Pseudomonas aeruginosa (PA), the most common pathogen isolated mainly in patients with cystic fibrosis, is particularly difficult to eradicate and is associated with acceleration of decline in lung function and with poorer prognosis. PA LPS is recognized by toll like receptors 4 (TLR4) and has been shown to induce lung inflammation in vivo. In addition, regulation of this process is essential for proper pathogen clearance and to prevent excessive inflammatory response resulting in tissue damage...
March 15, 2018: Shock
Jinming Zhu, Miao He, Chunling Ma, Fengyun Peng, Yuli Su, Lei Huang
BACKGROUND In this study, we aimed to investigate the expression of NOD-like receptor protein 3 (NLRP3) and caspase-1 in fetal membrane and placental tissues of patients with premature rupture of membrane (PROM), and to explore their role in PROM. MATERIAL AND METHODS Ninety women participated in this study: a control group of 30 healthy pregnant women, 30 with PPROM, and 30 with TPROM. Immunohistochemistry streptavidin-peroxidase (SP) assay was used to detect the protein expression of NLRP3 and caspase-1 in the fetal membrane and placental tissues...
March 16, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Fawaz Awad, Eman Assrawi, Camille Louvrier, Claire Jumeau, Irina Giurgea, Serge Amselem, Sonia-Athina Karabina
Photoaging and epithelial skin tumorigenesis are complex processes triggered mainly by UV radiation from chronic sun exposure. This leads to DNA damage and reactive oxygen species (ROS) production, which initiate an inflammatory response that alters cell structure and function. Changes in cell homeostasis and ROS production activate intracellular multiprotein platforms called inflammasomes. Inflammasomes nucleate around cytoplasmic receptors mainly of the NLR (nucleotide-binding domain and leucine-rich repeat) family and regulate caspase-1-dependant secretion of pro-inflammatory interleukin (IL)-1β and IL-18 cytokines, and an inflammatory form of death named pyroptosis...
March 12, 2018: Mechanisms of Ageing and Development
Ruiting Li, Jing Wang, Ruifang Li, Fangfang Zhu, Wenjuan Xu, Gan Zha, Guangzhen He, Huan Cao, Yimin Wang, Jiong Yang
The ATP/P2X7 axis of dendritic cells (DCs) mediates the activation of NLRP3 inflammasome and promotes secretion of interleukin (IL)-1β and IL-18 to induce T helper (Th) 2, Th17 differentiation in the pathogenesis of asthma. NLRP3 inflammasome also regulates high mobility protein 1 (HMGB1) release in DCs. Recent studies demonstrated the correlation between HMGB1 expression and airway inflammation and hyper-responsiveness (AHR) in asthma. However, the relationship between the ATP/P2X7-NLRP3 axis and HMGB1 in DCs in asthma is still unclear...
March 12, 2018: Experimental Cell Research
Takuya Wakamatsu, Suguru Yamamoto, Toru Ito, Yoko Sato, Koji Matsuo, Yoshimitsu Takahashi, Yoshikatsu Kaneko, Shin Goto, Junichiro James Kazama, Fumitake Gejyo, Ichiei Narita
In chronic kidney disease (CKD) patients, accumulation of uremic toxins is associated with cardiovascular risk and mortality. One of the hallmarks of kidney disease-related cardiovascular disease is intravascular macrophage inflammation, but the mechanism of the reaction with these toxins is not completely understood. Macrophages differentiated from THP-1 cells were exposed to indoxyl sulfate (IS), a representative uremic toxin, and changes in inflammatory cytokine production and intracellular signaling molecules including interleukin (IL)-1, aryl hydrocarbon receptor (AhR), nuclear factor (NF)-κ, and mitogen-activated protein kinase (MAPK) cascades as well as the NLRP3 inflammasome were quantified by real-time PCR, Western blot analysis, and enzyme-linked immunosorbent assay...
March 15, 2018: Toxins
Vahid Mirshafiee, Bingbing Sun, Chong Hyun Chang, Yu-Pei Liao, Wen Jiang, Jinhong Jiang, Xiangsheng Liu, Xiang Wang, Tian Xia, Andre E Nel
The liver and the mononuclear phagocyte system (MPS) is a frequent target for engineered nanomaterials (ENMs), either as a result of particle uptake and spread from primary exposure sites or systemic administration of therapeutic and imaging nanoparticles. In this study, we performed a comparative analysis of the toxicological impact of 29 metal oxide (MOx) nanoparticles (NPs), some commonly used in consumer products, in transformed or primary Kupffer cells (KCs) and hepatocytes. Not only did we observe differences between KC and hepatocytes, but also differences in the toxicological profiles of transition metal oxides (TMOs, e...
March 15, 2018: ACS Nano
Raffaella Mastrocola, Ilario Ferrocino, Erica Liberto, Fausto Chiazza, Alessia Sofia Cento, Debora Collotta, Giulia Querio, Debora Nigro, Valeria Bitonto, Juan Carlos Cutrin, Kalliopi Rantsiou, Mariaconcetta Durante, Emanuela Masini, Manuela Aragno, Chiara Cordero, Luca Cocolin, Massimo Collino
Despite clinical findings suggesting that the form (liquid versus solid) of the sugars may significantly affect the development of metabolic diseases, no experimental data are available on the impact of their formulations on gut microbiota, integrity and hepatic outcomes. In the present sudy, C57Bl/6j mice were fed a standard diet plus water (SD), a standard diet plus 60% fructose syrup (L-Fr) or a 60% fructose solid diet plus water (S-Fr) for 12 weeks. Gut microbiota was characterized through 16S rRNA phylogenetic profiling and shotgun sequencing of microbial genes in ileum content and related volatilome profiling...
February 13, 2018: Journal of Nutritional Biochemistry
Gregory B Lim
No abstract text is available yet for this article.
March 13, 2018: Nature Reviews. Cardiology
Yi Huang, Hua Jiang, Yun Chen, Xiaqiong Wang, Yanqing Yang, Jinhui Tao, Xianming Deng, Gaolin Liang, Huafeng Zhang, Wei Jiang, Rongbin Zhou
The dysregulation of NLRP3 inflammasome can cause uncontrolled inflammation and drive the development of a wide variety of human diseases, but the medications targeting NLRP3 inflammasome are not available in clinic. Here, we show that tranilast (TR), an old anti-allergic clinical drug, is a direct NLRP3 inhibitor. TR inhibits NLRP3 inflammasome activation in macrophages, but has no effects on AIM2 or NLRC4 inflammasome activation. Mechanismly, TR directly binds to the NACHT domain of NLRP3 and suppresses the assembly of NLRP3 inflammasome by blocking NLRP3 oligomerization...
March 12, 2018: EMBO Molecular Medicine
Wenbiao Wang, Feng Xiao, Pin Wan, Pan Pan, Yecheng Zhang, Fang Liu, Kailang Wu, Yingle Liu, Jianguo Wu
[This corrects the article DOI: 10.1371/journal.ppat.1006123.].
March 2018: PLoS Pathogens
Carmen Gonzalez-Hidalgo, Joaquin De Haro, Silvia Bleda, Cristina Cañibano, Ignacio Michel, Francisco Acin
NLRP1 and NLRP3 inflammasomes might differentially mediate the chronic inflammatory response in abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD). We measure differential relative gene expression of NLRP1 and NLRP3 inflammasomes in aortic tissues from 30 patients undergoing AAA open repair compared to aortic biopsies from 30 patients undergoing surgery to treat AOD. Aortic wall samples from autopsy without aortic disease were used as controls. NLRP3 was overexpressed in patients with AAA and AOD (RQ 1...
April 2018: Therapeutic Advances in Cardiovascular Disease
Fanfan Xu, Xinghua Qiu, Xinyan Hu, Yu Shang, Michal Pardo, Yanhua Fang, Junxia Wang, Yinon Rudich, Tong Zhu
Fine particulate matter (PM2.5 ) air pollution poses a major risk to human health worldwide, and absorbed chemicals play a key role in determining the toxicity of PM2.5 . After inhalation and entry into the lungs, PM2.5 components induce pro-inflammatory cytokines (e.g., interleukin (IL)-1β) in pulmonary cells. To test whether PM2.5 components induce IL-1β through signing pathways that include the toll-like receptor 4 (TLR4)/nuclear factor-κ-gene binding (NF-κB), nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3), we exposed the mouse macrophage cell-line RAW264...
March 8, 2018: Environmental Pollution
Manon Viaud, Stoyan Ivanov, Nemanja Vujic, Madalina Duta-Mare, Lazaro-Emilio Aira, Thibault Barouillet, Elsa Garcia, François Orange, Isabelle Dugail, Isabelle Hainault, Christian Stehlik, Sandrine Marchetti, Laurent Boyer, Rodolphe Guinamard, Fabienne Foufelle, Andrea E Bochem, Kees G Hovingh, Edward B Thorp, Emmanuel L Gautier, Dagmar Kratky, Paul A Da Silva-Jardine, Laurent Yvan-Charvet
<u>Rationale:</u> Macrophages face a substantial amount of cholesterol following the ingestion of apoptotic cells and the lysosomal acid lipase (LIPA) has a major role in hydrolyzing cholesteryl esters in the endocytic compartment. <u>Objective:</u> Here, we directly investigated the role of LIPA-mediated clearance of apoptotic cells both in vitro and in vivo. <u>Methods and Results:</u> We show that LIPA inhibition causes a defective efferocytic response due to impaired generation of 25-OHC and 27-OHC...
March 9, 2018: Circulation Research
Csaba Fekete, Csaba Vastagh, Ádám Dénes, Erik Hrabovszky, Gábor Nyiri, Imre Kalló, Zsolt Liposits, Miklós Sárvári
Microglia are instrumental for recognition and elimination of amyloid β1-42 oligomers (AβO), but the long-term consequences of AβO-induced inflammatory changes in the brain are unclear. Here, we explored microglial responses and transciptome-level inflammatory signatures in the rat hippocampus after chronic AβO challenge. Middle-aged Long Evans rats received intracerebroventricular infusion of AβO or vehicle for 4 weeks, followed by treatment with artificial CSF or MCC950 for the subsequent 4 weeks. AβO infusion evoked a sustained inflammatory response including activation of NF-κB, triggered microglia activation and increased the expression of pattern recognition and phagocytic receptors...
March 6, 2018: Neuroscience
Lan H Chu, Mohanalaxmi Indramohan, Rojo A Ratsimandresy, Anu Gangopadhyay, Emily P Morris, Denise M Monack, Andrea Dorfleutner, Christian Stehlik
Lipopolysaccharide (LPS) of Gram-negative bacteria can elicit a strong immune response. Although extracellular LPS is sensed by TLR4 at the cell surface and triggers a transcriptional response, cytosolic LPS binds and activates non-canonical inflammasome caspases, resulting in pyroptotic cell death, as well as canonical NLRP3 inflammasome-dependent cytokine release. Contrary to the highly regulated multiprotein platform required for caspase-1 activation in the canonical inflammasomes, the non-canonical mouse caspase-11 and the orthologous human caspase-4 function simultaneously as innate sensors and effectors, and their regulation is unclear...
March 8, 2018: Nature Communications
Tao Ding, Shaofei Wang, Xuyao Zhang, Wenjing Zai, Jiajun Fan, Wei Chen, Qi Bian, Jingyun Luan, Yilan Shen, Yanda Zhang, Dianwen Ju, Xiaobin Mei
BACKGROUND: Diabetic nephropathy (DN), the leading cause of end-stage renal disease, is acknowledged as an independent risk factor for cardiovascular disease, which underlines the urgent need for new medications to DN. Dihydroquercetin (DHQ), an important natural dihydroflavone, exerts significant antioxidant, anti-inflammatory, and antifibrotic properties, but its effects on DN have not been investigated yet. PURPOSE: We aimed to explore the kidney protection effects of DHQ on DN rats induced by high-fat diet/streptozotocin in vivo and the underlying mechanisms of DHQ on renal cells including HBZY-1 and HK2 exposed to high glucose in vitro...
March 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Kang Wang, Lei Hu, Jian-Kang Chen
Recent preclinical and clinical evidence suggests that hyperuricemia (HU) is an independent risk factor for metabolic syndrome, hypertension, cardiovascular disease and chronic kidney disease. Receptor-interacting protein 3 (RIP3) is an important contributor in inducing programmed necrosis, representing a newly identified mechanism of cell death combining features of both apoptosis and necrosis. In our study, RIP3 was strongly expressed in mice with hyperuricemia. RIP3 deficiency attenuated hyperuricemia in mice, evidenced by reduced serum uric acid and creatinine and enhanced urinary uric acid and creatinine, as well as the improved histological alterations in renal sections...
March 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Zhenjian He, Jiahui Chen, Shu An, Xinhuai Dong, Jianchen Yu, Shihao Zhang, Yun Wu, Ge Li, Yu Zhang, Jueheng Wu, Xun Zhu, Mengfeng Li
Zika virus (ZIKV) is a mosquito-borne virus that has been identified as a cause of several severe disease manifestations, including congenital microcephaly and Guillain-Barré syndrome, meningoencephalitis and myelitis. Previous studies showed that ZIKV-infected patients exhibited elevated plasma levels of interleukin-1β (IL-1β), indicating that ZIKV may activate inflammasomes. However, the molecular basis for its viral pathogenesis remains poorly understood. In this current study, we found that ZIKV infection caused severe inflammatory pathological changes and promoted IL-1β production in vitro as well as in vivo...
March 6, 2018: Journal of Infectious Diseases
Richard Conway, Geraldine M McCarthy
PURPOSE OF REVIEW: Osteoarthritis (OA) is the most common form of joint disease globally and is associated with significant morbidity and disability. Increasing evidence points to an important inflammatory component in the development and progression of OA. The precise pathways involved in OA inflammatory processes remain to be clarified. Basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP) crystals can induce inflammation and arthritis and recent studies point to a potential pathogenic role in OA...
March 8, 2018: Current Rheumatology Reports
Jorge David Rojas Márquez, Yamile Ana, Ruth Eliana Baigorrí, Cinthia Carolina Stempin, Fabio Marcelo Cerban
The causative agent of Chagas' disease, Trypanosoma cruzi , affects approximately 10 million people living mainly in Latin America, with macrophages being one of the first cellular actors confronting the invasion during T. cruzi infection and their function depending on their proper activation and polarization into distinct M1 and M2 subtypes. Macrophage polarization is thought to be regulated not only by cytokines and growth factors but also by environmental signals. The metabolic checkpoint kinase mammalian target of rapamycin (mTOR)-mediated sensing of environmental and metabolic cues influences macrophage polarization in a complex and as of yet incompletely understood manner...
2018: Frontiers in Immunology
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