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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
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
Maozhi Hu, Weixin Zhao, Hongying Li, Jie Gu, Qiuxiang Yan, Xiaohui Zhou, Zhiming Pan, Guiyou Cui, Xinan Jiao
BACKGROUND: Enhancing caspase-1 activation in macrophages is helpful for the clearance of intracellular bacteria in mice. Our previous studies have shown that EscI, an inner rod protein of type III system in E. coli can enhance caspase-1 activation. The purpose of this study was to further analyze the prospect of EscI in the vaccine design. RESULTS: A recombinant Salmonella expressing SspH2-EscI fusion protein using the promotor of Salmonella effector SspH2, X4550(pYA3334-P-SspH2-EscI), was constructed...
March 9, 2018: BMC Veterinary Research
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
Arkadiy Reunov, Anatoliy Reunov, Evgenia Pimenova, Yulia Reunova, Ekaterina Menchinskaiya, Larisa Lapshina, Dmitry Aminin
An expression of calpain and caspase-1 as well as the concomitant ultrastructural alterations were investigated during necrosis of the mouse Ehrlich ascites carcinoma. The calpain expression was registered at 0 h and 1 h although caspase-1 did not induce any signals during these time periods. The rise of the cytoplasmic lytic zones contacted by calpain antibodies was identified as a morphologic event corresponding to the expression of calpain. Lytic zone's distribution followed by the appearance of the calpain/caspase-1 clusters assigned for lysis of the Golgi vesicles and ER...
March 5, 2018: Gene
Yong-Huai Li, Xiang Wei, Shuang Ji, Shu-Yu Gui, Su-Mei Zhang
The present study aimed to investigate the effects of nucleotide-binding domain leucine-rich repeat protein (NLRP)1/NLRP3 inflammasome pathways on latent viral infection of the respiratory tract. A total of 55 BALB/c mice were assigned to the control, bleomycin (BLM)‑treated, murine cytomegalovirus (MCMV), MCMV+BLM and MCMV+BLM+CD4+ T‑cell groups. The viral loads were detected in the salivary glands, kidney, liver and lung tissues via polymerase chain reaction (PCR). The weight, lung coefficient and hydroxyproline (HYP) were detected...
February 28, 2018: International Journal of Molecular Medicine
Asha Lekshmi, Shankara Narayanan Varadarajan, Santhik Subhasingh Lupitha, Mydhily Nair, Aneesh Chandrasekharan, T R Santhoshkumar
Recent cell biology studies reveal that a cell can die through multiple pathways via distinct signaling mechanisms. Among these, apoptosis and necrosis are two distinct cell death pathways, and their detection and discrimination is vital in the drug discovery process and in understanding diverse biological processes. Although sensitive assays for apoptosis and necrosis are available, it is extremely difficult to adapt any of these methods to discriminate apoptosis-inducing stimuli from necrosis-inducing stimuli because of the acquisition of secondary necrosis by apoptotic cells when they are not phagocytosed...
February 21, 2018: Current Protocols in Toxicology
Haixia Zhang, Kuangpeng Liu, Zhixiao Xue, Huijuan Yin, Huajiang Dong, Wendong Jin, Xiafei Shi, Han Wang, Hai Wang
This study evaluated the effects and mechanism of action of combining irreversible electroporation (IRE) and photodynamic therapy (PDT) in breast cancer cells in vitro and in vivo . Jin's formula was used to assess killing efficacy of different IRE+PDT dosing combinations in breast cancer MCF-7 cells. Flow cytometry, high-content imaging, and confocal laser scanning microscopy were used to detect apoptosis. qRT-PCR and western blotting were used to evaluate expression of apoptosis-related genes and proteins...
2018: American Journal of Translational Research
Dengming Lai, Jing Tang, Linsong Chen, Erica K Fan, Melanie J Scott, Yuehua Li, Timothy R Billiar, Mark A Wilson, Xiangming Fang, Qiang Shu, Jie Fan
Group 2 innate lymphoid cells (ILC2) are one of three subgroups of innate lymphoid cells (ILC1, ILC2, and ILC3), and the major ILC population detected in the lungs. The function of ILC2 in the regulation of lung inflammation remains unclear. In the current study, we explored an important role of ILC2 in protecting lung endothelial cell (EC) from pyroptosis in sepsis-induced acute lung inflammation and the underlying mechanism. Using a cecal ligation and puncture (CLP) mouse sepsis model, we demonstrated that IL-33, which is released in response to sepsis, acting through its receptor ST2 mediates ILC2 expansion in the lungs...
March 6, 2018: Cell Death & Disease
Yochai Birnbaum, Mandeep Bajaj, Hsiu-Chiung Yang, Yumei Ye
BACGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 inhibitors (DPP4I) are used to treat type 2 diabetes (T2DM). DPP4 inhibitors (DPP4) attenuate Nlrp3 inflammasome activation in the kidney. SGLT2 inhibition reduces inflammation and attenuates the progression of diabetic nephropathy (DN). The effects of dapagliflozin (Dapa) on the activation of the Nlrp3 inflammasome and the combined effect of SGLT2 and DPP4 on T2DM-induced inflammasome activation and progression of DN have not been previously studied...
March 5, 2018: Cardiovascular Drugs and Therapy
Cuong Thach Nguyen, Shyam Kishor Sah, Tae-Yoon Kim
Propionibacterium acnes is a well-known commensal bacterium that plays an important role in the pathogenesis of acne and chronic inflammatory skin disease. In this study, we investigated the effect of superoxide dismutase 3 (SOD3) on P. acnes- or peptidoglycan (PGN)-induced inflammation in vitro and in vivo. Our data demonstrated that SOD3 suppressed toll-like receptor-2 (TLR-2) expression in P. acnes- or PGN-treated keratinocytes and sebocytes. Moreover, we found that SOD3 suppressed the expressions of phosphorylated nuclear factor-κB (NF-κB) and p38 in P...
March 5, 2018: Scientific Reports
Ailing Sui, Yisheng Zhong, Anna M Demetriades, Qing Lu, Yujuan Cai, Yushuo Gao, Yanji Zhu, Xi Shen, Bing Xie
PURPOSE: To assess the effect of inhibiting integrin α5β1 by ATN-161 on vascular endothelial growth factor (VEGF)-induced neovascularization (NV) and leakage causing retinal detachment in adult Tet/opsin/VEGF transgenic mice, and characterize the underlying mechanism of its function. METHOD: Retinas from adult Tet/opsin/VEGF transgenic mice and human retinal endothelial cells (HRECs) exposed to VEGF (treated with ATN-161 or PBS) were used to carry out immunofluorescence, RT-PCR and western blot to examine expression levels of integrin α5β1 and the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome...
March 3, 2018: Graefe's Archive for Clinical and Experimental Ophthalmology
Gagandeep Kaur, Prathyusha Bagam, Rakeysha Pinkston, Dhirendra P Singh, Sanjay Batra
Chronic obstructive pulmonary disease (COPD) is a progressive, life-threatening disease that causes irreversible lung damage. Cigarette smoking is the chief etiologic factor for the commencement of this condition. Despite constant efforts to develop therapeutic interventions and to ascertain the molecular mechanism leading to the pathophysiology of this disease, much remains unknown. However, pattern recognition receptor (PRRs), i.e., Toll-like-receptors (TLRs) and NOD-like receptors (NLRs) are believed to play important roles in this disease and could serve as effective therapeutic targets...
February 28, 2018: Toxicology
Ömer Hazman, Mehmet Fatih Bozkurt, Abdurrahman Fatih Fidan, Fadime Erkan Uysal, Sefa Çelik
The development of treatment protocols that can reduce side effects in chemotherapy applications is extremely important in terms of cancer treatment. In this context, it was aimed to investigate the effects of boric acid and borax on cisplatin toxicity (nephrotoxicity) in rats. In the experimental phase, eight groups were formed from rats. Boric acid and borax were given to the treatment groups with three different doses using gavage. On the fifth day of the study, cisplatin (10 mg/kg) was administered to all rats except the control group...
March 2, 2018: Inflammation
Zhili Rao, Feng Xu, Taoqun Wen, Feng Wang, Wentao Sang, Nan Zeng
The essential oils from Rimulus cinnamon (EORC) have anti-inflammation activities, but the effects of EORC on endotoxin poisoning mice remain to be explored, the mechanism is still unclear. This study was designed to investigate the protective effects and mechanism of EORC on lipopolysaccharide (LPS)-induced endotoxin poisoning mice. Pre-treatment with EORC decreased the production of pro-inflammatory cytokines (Interleukin-1β, Interleukin-18, Interleukin-5, and Interferon-γ) and chemokines (Monocyte chemotactic protein-1, Macrophage colony-stimulating factor, and Macrophage inflammatory protein-1β) in serum of endotoxin poisoning mice...
February 27, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jing Cheng, Fei Xue, Meng Zhang, Cheng Cheng, Lei Qiao, Jing Ma, Wenhai Sui, Xingli Xu, Chengjiang Gao, Panpan Hao, Meng Zhang, Yun Zhang
Tripartite motif-containing protein 31 (TRIM31), an E3 ubiquitin ligase of the tripartite motif family, plays an important role in the innate immune response. It can reduce the activity of the nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome. However, little information is about glucose metabolic health of TRIM31-deficient mice, and investigations about gut microbiota in TRIM31-deficient mice is limited. Thus, we aimed to compare glucose metabolic parameters, gut microbiota composition and inflammatory cytokine levels between TRIM31-/- and wild-type (WT) mice, and further investigate whether or not certain gut microbiota taxon correlates with specific metabolic parameters and inflammation cytokines in TRIM31-deficient mice...
2018: Frontiers in Physiology
Yadong Zhai, Xiangbao Meng, Tianyuan Ye, Weijie Xie, Guibo Sun, Xiaobo Sun
Diabetes is associated with a high risk of developing cognitive dysfunction and neuropsychiatric disabilities, and these disease symptomsare termed diabetic encephalopathy (DEP). Inflammation is involved in the development of DEP. The cleavage and maturation of the proinflammatory cytokine interleukin (IL)-1β is regulated by the NLRP3 inflammasome. Obese and type 2 diabetic db/db mice show anxiety- and depression-like behaviors and cognitive disorders associated with hippocampal inflammation. The purpose of this study was to explore the role of NLRP3 inflammasome in DEP...
February 27, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Ming Chen, Ju-Tao Wang, Hua-Wu Gao, Sheng-Ping Lei, Yong-Heng Zhu
This paper was aimed to investigate the relationship between autophagy and NLRP3 inflammasome activation by studying the effect oftotal flavonoids in Scutellaria barbata (TF-SB) on autophagy in tumor cells and NLRP3 inflammasome, and to provide experimental evidence for further study of the anti-tumor mechanism of TF-SB. Mielanoma models were established by inoculating B16-F1 cell line to mice, and then were randomly divided into 5 groups (n=10 in each group): model control, positive control control(Rap, 1...
December 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Enquan Xu, Jianuo Liu, Han Liu, Xiaobei Wang, Huangui Xiong
Methamphetamine (Meth) is an addictive psychostimulant abused worldwide. Ample evidence indicate that chronic abuse of Meth induces neurotoxicity via microglia-associated neuroinflammation and the activated microglia present in both Meth-administered animals and human abusers. The development of anti-neuroinflammation as a therapeutic strategy against Meth dependence promotes research to identify inflammatory pathways that are specifically tied to Meth-induced neurotoxicity. Currently, the exact mechanisms for Meth-induced microglia activation are largely unknown...
February 28, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
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