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Caspase 11

Brice Lagrange, Sacha Benaoudia, Pierre Wallet, Flora Magnotti, Angelina Provost, Fanny Michal, Amandine Martin, Flaviana Di Lorenzo, Bénédicte F Py, Antonio Molinaro, Thomas Henry
Caspase-4/5 in humans and caspase-11 in mice bind hexa-acylated lipid A, the lipid moeity of lipopolysaccharide (LPS), to induce the activation of non-canonical inflammasome. Pathogens such as Francisella novicida express an under-acylated lipid A and escape caspase-11 recognition in mice. Here, we show that caspase-4 drives inflammasome responses to F. novicida infection in human macrophages. Caspase-4 triggers F. novicida-mediated, gasdermin D-dependent pyroptosis and activates the NLRP3 inflammasome. Inflammasome activation could be recapitulated by transfection of under-acylated LPS from different bacterial species or synthetic tetra-acylated lipid A into cytosol of human macrophage...
January 16, 2018: Nature Communications
Pei Wu, Xin Zheng, Xiao-Qiu Zhou, Wei-Dan Jiang, Yang Liu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Yong-An Zhang, Lin Feng
The aim of this study was to assess the effects of dietary pyridoxine (PN) deficiency on intestinal antioxidant capacity, cell apoptosis and intercellular tight junction in young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (231.85 ± 0.63 g) were fed six diets containing graded levels of PN (0.12-7.48 mg/kg diet) for 10 weeks. At the end of the feeding trial, the fish were challenged with Aeromonas hydrophila for 2 weeks. The results showed that compared with the optimal PN level, PN deficiency (1) increased the contents of reactive oxygen species (ROS), malondialdehyde (MDA) and protein carbonyl (PC), decreased the activities and mRNA levels of antioxidant enzymes such as copper, zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) (P < ...
January 12, 2018: Fish & Shellfish Immunology
R C Yue, X L Yang, R Y Zhang, S Liu, J Liu, J Zeng, H Liang, W Wang, H X Hu, C Y Zeng
Objective: To investigate the effect and related mechanism of salvianolate on myocardial ischemia-reperfusion (I/R) injury in rats. Methods: Thirty-six adult Sprague-Dawley rats were divided into three groups (n=12 each) using random number table method: control group (coronary artery was not ligated) , I/R group (myocardial I/R model was established by ligation and opening of left anterior descending coronary artery) , and salvianolate+I/R group (5 mg/kg of salvianolate was injected through the tail vein at the time of reperfusion) ...
December 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
Fu-Shui Liu, Fan-Yuan Zhou, Yi Zhang, Chang-Qing Guo
OBJECTIVE: To observe the effect of acupotomy therapy on mRNA expressions of Bcl-2, Bax , Caspase-3 in posterior cervical extensor muscles in cervical spondylosis rabbits, and explore its mechanisms for apoptosis of cervical muscles. METHODS: New Zealand rabbits were randomly divided into normal, model, electroacupuncture (EA) and acupotomy groups, 6 in each group. The cervical spondylosis model was established by forced head-bowing for a long term. After model establishment, acupotomy was used at the trapezius muscle starting point and attachment site of sternocleidomastoid muscle, etc...
December 25, 2017: Zhen Ci Yan Jiu, Acupuncture Research
Kornelia Ellwanger, Emily Becker, Ioannis Kienes, Anna Sowa, Yvonne Postma, Yamel Cardona Gloria, Alexander N R Weber, Thomas A Kufer
Mammalian NLR proteins contribute to the regulation and induction of innate and adaptive immunity in mammals although the function of about half of the currently identified NLR proteins remains poorly characterized. Here we analysed the function of the primate-specific NLRP11 gene product. We show that NLRP11 is highly expressed in immune cells, including myeloid cells, B cells and some B cell lymphoma lines. Overexpression of NLRP11 in human cells did not trigger key innate immune signalling pathways including NF-κB and type I interferon responses...
January 4, 2018: Journal of Biological Chemistry
Hong Qi, Yu Jiang, Zhiyong Yin, Ke Jiang, Linxi Li, Jianwei Shuai
The formation of a heptameric apoptosome is a crucial event in the intrinsic cell death pathway. Considerable progress has been made towards unraveling the constituents and the structure of the apoptosome as well as the mechanism of apoptosome-mediated caspase-9 activation. However, a significant gap remains in the understanding of this process, i.e., how seven Apaf-1·cytochrome c complexes stepwisely assemble into an apoptosome. Here, we construct a biophysical model that incorporates current biochemical knowledge about the formation of apoptosome...
January 4, 2018: Physical Chemistry Chemical Physics: PCCP
Liedao Yu, Shuo Wang, Xiangjin Lin, Yang Lu, Pengcheng Gu
Liver cancer is the sixth most common malignant tumour and ranks in the top three cancers with regard to mortality due to metastasis and postsurgical recurrence. It is significant to understand the mechanisms underlying liver cancer for diagnosis and treatment. Cumulative evidence suggests that the abnormal regulation of microRNAs (miRNAs/miRs) may contribute to the development and metastasis of cancer. miR‑124a acts as a tumour suppressor in osteosarcoma, endometrial carcinoma, prostate cancer, and glioblastoma...
December 27, 2017: Molecular Medicine Reports
Di Wu, Da-Wei Zhao, Yong-Qi Li, Wei-Guo Shi, Qi-Liang Yin, Zheng-Kun Tu, Ying-Ying Yu, Bo-Hua Zhong, Hong Yu, Wan-Guo Bao
Camptothecin (CPT) is a cytotoxic quinoline alkaloid that is used clinically as an anticancer drug. However, the clinical application of CPT is limited due to its low solubility as well as serious and unfathomable side-effects. In the present study, we created a novel 10-hydroxy CPT prodrug, ZBH-ZM‑06. Its cellular cytotoxic activity was analyzed in terms of cellular viability, acetylcholinesterase (AchE) inhibition, DNA relaxation, cellular cycling and apoptosis properties. Our results showed that the AchE inhibition rate of 10 µmol/l ZBH-ZM-06 was 12...
February 2018: Oncology Reports
Aynur Gultekin, Halil Ibrahim Tanriverdi, Sevinc Inan, Omer Yilmaz, Cuneyt Gunsar, Aydin Sencan
PURPOSE: Testis torsion is a surgical emergency, and sometimes we cannot sufficiently prevent injury even surgical detorsion of the testis is performed in the appropriate time period due to some reasons such as tissue edema. In this experimental study, we investigated the effect of tunica albuginea incision (TAI) on testicular torsion-detorsion model (TDM). MATERIALS AND METHODS: Twenty four male rats were used. The rats were randomly divided into three groups. In Group I, testicular torsion (TT) of 720° was created...
December 17, 2017: Urology Journal
Paromita Bhattacharjee, Tapas Ghosh, Sarita Sarkar, Prateek Pandya, Kakali Bhadra
The work focuses towards interaction of harmaline, with nucleic acids of different motifs by multispectroscopic and calorimetric techniques. Findings of this study suggest that binding constant varied in the order single-stranded (ss) poly(A) > double-stranded calf thymus (CT) DNA > double-stranded poly(G)·poly(C) > clover leaf tRNAPhe . Prominent structural changes of ss poly(A), CT DNA, and poly(G)· poly(C) with concomitant induction of optical activity in the bound achiral alkaloid molecule was observed, while with tRNAPhe , very weak induced circular dichroism perturbation was seen...
December 15, 2017: Journal of Molecular Recognition: JMR
Kristen T Crowell, Samantha Moreno, Jennifer L Steiner, Catherine S Coleman, David I Soybel, Charles H Lang
BACKGROUND: Cardiac dysfunction is a common manifestation of sepsis and is associated with early increases in inflammation and decreases in myocardial protein synthesis. However, little is known regarding the molecular mechanisms regulating protein homeostasis during the recovery phase after the removal of the septic nidus. Therefore, the purpose of this study was to investigate diverse signal transduction pathways that regulate myocardial protein synthesis and degradation. METHODS: Adult male C57BL/6 mice were used to identify potential mechanisms mediating the acute (24 h) effect of cecal ligation and puncture (CLP) as well as long-term changes that manifest during the chronic (10 d) recovery phase...
December 13, 2017: Shock
Hong-Jian Zhang, Guo-Rui Zhang, Hu-Ri Piao, Zhe-Shan Quan
In the present study, three series of novel celastrol derivatives were designed and synthesised by modifying the carboxylic acid at the 20th position with amino acid, amine, and triazole derivatives. All the synthesised compounds were screened for their anticancer activities using MTT assay against AGS, MGC-803, SGC-7901, HCT-116, A549, HeLa, BEL-7402, and HepG-2 cell lines. Most of the synthesised compounds exhibited potent antiproliferative effects. The most promising compound 3-Hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic amide, N-(R)-methyl-3-(1H-indol-2-yl)propanoate (11) showed considerable high anticancer activity against AGS cell lines, with an IC50 value of 0...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
Pei Wu, Li Tian, Xiao-Qiu Zhou, Wei-Dan Jiang, Yang Liu, Jun Jiang, Fei Xie, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Juan Yang, Yong-An Zhang, He-Qun Shi, Lin Feng
This study evaluated the effect of dietary sodium butyrate (SB) supplementation on the intestinal physical barrier function of young grass carp (Ctenopharyngodon idella). The fish were fed one powdery sodium butyrate (PSB) diet (1000.0 mg kg-1 diet) and five graded levels of microencapsulated sodium butyrate (MSB) diets: 0.0 (control), 500.0, 1000.0, 1500.0 and 2000.0 mg kg-1 diet for 60 days. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila to explore the effect of SB supplementation on intestinal physical barrier function and the potential mechanisms in fish...
December 5, 2017: Fish & Shellfish Immunology
Yumei Liu, Thi Phuong Anh Nguyen, Menghua Chen, Lu Xie
OBJECTIVE: To study the effect of tea polyphenols (TP) on c-Jun N-terminal kinase 1/2 (JNK1/2) phosphorylation and cell apoptosis in brain tissues in rats with cardiac arrest (CA) following cardiopulmonary resuscitation (CPR). METHODS: Healthy male Sprague-Dawley (SD) rats were randomly divided into sham group (n = 6), CA group (n = 12), and TP group (n = 12). The rats in CA and TP groups were induced ventricular fibrillation (VF) via esophagus stimulation with alternating current...
December 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Corentin Lasseaux, Marie-Pierre Fourmaux, Mathias Chamaillard, Lionel Franz Poulin
Emergency monocytopoiesis is an inflammation-driven hematological process that supplies the periphery with monocytes and subsequently with macrophages and monocyte-derived dendritic cells. Yet, the regulatory mechanisms by which early bone marrow myeloid progenitors commit to monocyte-derived phagocytes during endotoxemia remains elusive. Herein, we show that type I interferons signaling promotes the differentiation of monocyte-derived phagocytes at the level of their progenitors during a mouse model of endotoxemia...
December 5, 2017: Scientific Reports
Baiyang You, Yanbo Liu, Jia Chen, Xiao Huang, Huihui Peng, Zhaoya Liu, Yixing Tang, Kai Zhang, Qian Xu, Xiaohui Li, Guangjie Chen, Ruizheng Shi, Guogang Zhang
Aims: Reactive oxygen species (ROS) play essential roles in the pulmonary vascular remodelling associated with hypoxia-induced pulmonary hypertension (PH). Vascular peroxidase 1 (VPO1) is a newly identified haeme-containing peroxidase that accelerates oxidative stress development in the vasculature. This study aimed to determine the potential role of VPO1 in hypoxia-induced PH-related vascular remodelling. Methods and results: The vascular morphology and VPO1 expression were assessed in the pulmonary arteries of Sprague-Dawley (SD) rats...
November 27, 2017: Cardiovascular Research
Stephan R Vavricka, Jose A Galván, Heather Dawson, Alex Soltermann, Luc Biedermann, Michael Scharl, Alain M Schoepfer, Gerhard Rogler, Mareike B Prinz Vavricka, Luigi Terracciano, Alexander Navarini, Inti Zlobec, Alessandro Lugli, Thomas Greuter
Background: Pathogenesis of cutaneous extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) remains elusive. Efficacy of anti-TNF agents suggests TNF-dependent mechanisms. The role of other biologics such as anti-integrins or JAK-inhibitors is not yet clear. Methods: We performed immunohistochemistry for TNFα, NFκB, STAT1/STAT3, MAdCAM1, CD20/68, caspase 3/9, IFNγ, Hsp-27/70 on 240 intestinal (55 controls, 185 IBD) and 64 skin biopsies (11 controls, 18 Erythema nodosum (EN), 13 Pyoderma gangenosum (PG), 22 psoriasis)...
November 22, 2017: Journal of Crohn's & Colitis
Yue Zhao, Jianjin Shi, Feng Shao
Gasdermin-D (also known as GSDMD), the newly identified executioner of pyroptotic cell death, is cleaved by activated caspase-1 downstream of canonical inflammasome activation or caspase-4, 5, and 11 upon their ligation and activation by cytosolic LPS. Upon a single cleavage between the two domains in Gasdermin-D, the N-terminal domain binds to membrane lipids and lyses cells by forming pores of an inner diameter of 10-14 nm within the membrane. The inter-domain cleavage of Gasdermin-D is a reliable marker for the activation of inflammatory caspases and cell pyroptosis...
2018: Methods in Molecular Biology
Nagaraj Kerur, Shinichi Fukuda, Daipayan Banerjee, Younghee Kim, Dongxu Fu, Ivana Apicella, Akhil Varshney, Reo Yasuma, Benjamin J Fowler, Elmira Baghdasaryan, Kenneth M Marion, Xiwen Huang, Tetsuhiro Yasuma, Yoshio Hirano, Vlad Serbulea, Meenakshi Ambati, Vidya L Ambati, Yuji Kajiwara, Kameshwari Ambati, Shuichiro Hirahara, Ana Bastos-Carvalho, Yuichiro Ogura, Hiroko Terasaki, Tetsuro Oshika, Kyung Bo Kim, David R Hinton, Norbert Leitinger, John C Cambier, Joseph D Buxbaum, M Cristina Kenney, S Michal Jazwinski, Hiroshi Nagai, Isao Hara, A Phillip West, Katherine A Fitzgerald, SriniVas R Sadda, Bradley D Gelfand, Jayakrishna Ambati
Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D-dependent interleukin-18 secretion...
November 27, 2017: Nature Medicine
Xueyan Dai, Chenghong Xing, Huabin Cao, Junrong Luo, Tiancheng Wang, Ping Liu, Xiaoquan Guo, Guoliang Hu, Caiying Zhang
Cadmium (Cd) and high Molybdenum (Mo) can lead to adverse reactions on animals, but the co-induced toxicity of Mo and Cd to liver in ducks was not well understood. To investigate the co-induced toxic effects of Mo combined with Cd on mitochondrial oxidative stress and apoptosis in duck livers. 240 healthy 11-day-old ducks were randomly divided into 6 groups (control, LMo group, HMo group, Cd group, LMoCd group and HMoCd group). After being treated for 30, 60, 90 and 120 days, liver mitochondrial antioxidant indexes, ceruloplasmin (CP), metallothionein (MT), Bak-1 and Caspase-3 genes mRNA expression levels, and ultrastructural changes were evaluated...
November 14, 2017: Chemosphere
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