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Eugenia Roupakia, Georgios Markopoulos, Evangelos Kolettas
Liu and colleagues investigated the expression of matrix matalloproteinases (MMPs) in human periodontal ligament fibroblasts (hPDLFs) regulated by interleukin-12 (IL-12), a cytokine implicated in inflammatory and immune responses. They showed that IL-12 activates canonical NF-kappaB signalling leading to increased expression of MMP-1 (Interstitial collagenase), MMP-3 (stromelysin 1) and MMP-13 (collagenase 3), and to a smaller reduction in the expression of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) at both mRNA and protein levels, with corresponding changes in the secreted levels of these extracellular matrix-remodelling and immune regulatory metalloproteinases...
March 19, 2018: Bioscience Reports
Yixi Chen, Jianping Cao, Qihui Zhao, Haiyong Luo, Yiguang Wang, Wenjian Dai
Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However, little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB (NF-κB) signaling pathway, and atherosclerotic lesion macrophage content...
March 2018: Korean Journal of Physiology & Pharmacology
Patryk Janus, Katarzyna Szołtysek, Gracjana Zając, Tomasz Stokowy, Anna Walaszczyk, Wiesława Widłak, Bartosz Wojtaś, Bartłomiej Gielniewski, Marta Iwanaszko, Rosemary Brown, Simon Cockell, Neil D Perkins, Marek Kimmel, Piotr Widlak
The NF-κB transcription factors are activated via diverse molecular mechanisms in response to various types of stimuli. A plethora of functions associated with specific sets of target genes could be regulated differentially by this factor, affecting cellular response to stress including an anticancer treatment. Here we aimed to compare subsets of NF-κB-dependent genes induced in cells stimulated with a pro-inflammatory cytokine and in cells damaged by a high dose of ionizing radiation (4 and 10 Gy). The RelA-containing NF-κB species were activated by the canonical TNFα-induced and the atypical radiation-induced pathways in human osteosarcoma cells...
February 21, 2018: Cellular Signalling
Moritz F Eissmann, Christine Dijkstra, Merridee A Wouters, David Baloyan, Dmitri Mouradov, Paul M Nguyen, Mercedes Davalos-Salas, Tracy L Putoczki, Oliver M Sieber, John M Mariadason, Matthias Ernst, Frederick Masson
Interleukin 33 (IL33) is an inflammatory cytokine released during necrotic cell death. The epithelium and stroma of the intestine express large amounts of IL33 and its receptor St2. IL33 is therefore continuously released during homeostatic turnover of the intestinal mucosa. Although IL33 can prevent colon cancer associated with inflammatory colitis, the contribution of IL33 signaling to sporadic colon cancer remains unknown. Here, we utilized a mouse model of sporadic colon cancer to investigate the contribution of IL33 signaling to tumorigenesis in the absence of pre-existing inflammation...
February 20, 2018: Cancer Immunology Research
Xiaotao Li, Qingwei Wang, Xiao Gao, Tong Yu, Lei Yuan, Jie Dai, Weicang Wang, Geng Chen, Chan Jiao, Wang Zhou, Quan Huang, Long Cui, Pei Zhang, Robb E Moses, Jianhua Yang, Fengyuan Chen, Junjiang Fu, Jianru Xiao, Lei Li, Yongyan Dang
PURPOSE: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers closely associated with inflammation and hyperactive growth. We have previously demonstrated a regulatory circuit between the proteasome activator REGγ and NF-kappaB (NF-κB) during colon inflammation, known to be important in the development of colitis-associated cancer as well as sporadic CRC. How the inflammatory microenvironment affects the Hippo pathway during CRC development is largely unknown. EXPERIMENTAL DESIGN: Here, we used REGγ deficient colon cancer cell lines, REGγ knockout mice and human CRC samples to identify the novel molecular mechanism by which REGγ functions as an oncoprotein in the development of colorectal cancer...
February 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Hui Zhao, Meimei Bu, Binglu Li, Yong Zhang
Desfluraneis a widely-used general anesthetics. However, recent reports showed its significant side effect in the nervous system. Desflurane could lead to the neuronal death and affect the working memory. Unfortunately, the mechanism underlying the action of desflurane is still not clear and there is still no potent medicine to prevent the lesion in the central nervous system caused by general anesthetics. In this study, we found α-lipoic acid, an antioxidant exerting protective effect on multiple cells tissues, could resist the neurotoxicity caused by desflurane exposure...
February 2018: Tissue & Cell
Nils Wagner, Scott Dieteren, Niklas Franz, Kernt Köhler, Katharina Mörs, Luka Nicin, Julia Schmidt, Mario Perl, Ingo Marzi, Borna Relja
BACKGROUND: The treatment of patients with multiple trauma including blunt chest/thoracic trauma (TxT) and hemorrhagic shock (H) is still challenging. Numerous studies show detrimental consequences of TxT and HS resulting in strong inflammatory changes, organ injury and mortality. Additionally, the reperfusion (R) phase plays a key role in triggering inflammation and worsening outcome. Ethyl pyruvate (EP), a stable lipophilic ester, has anti-inflammatory properties. Here, the influence of EP on the inflammatory reaction and liver injury in a double hit model of TxT and H/R in rats was explored...
2018: PloS One
Nan Yu, Sinian Wang, Xiujun Song, Ling Gao, Wei Li, Huijie Yu, Chuanchuan Zhou, Zhenxia Wang, Fengsheng Li, Qisheng Jiang
For dendritic cells (DCs) to initiate an immune response, their ability to migrate and to produce interleukin-12 (IL-12) is crucial. It has been previously shown that low-dose radiation (LDR) promoted IL-12 production by DCs, resulting in increased DC activity that contributed to LDR hormesis in the immune system. However, the molecular mechanism of LDR-induced IL-12 production, as well as the effect of LDR on DC migration capacity require further elucidation. Using the JAWSII immortalized mouse dendritic cell line, we showed that in vitro X-ray irradiation (0...
February 8, 2018: Radiation Research
Liyan Wu, Zujin Luo, Jinxu Zheng, Peng Yao, Zhenyan Yuan, Xiaohong Lv, Jing Zhao, Min Wang
IL-33 played an important role in inflammatory diseases as evidenced by their high levels of expression in diseased tissues. Previous studies showed that IL-33/ST2L signal transduction pathway participated in epithelial-mesenchymal transition (EMT) of A549 cells. Cytokine IL-1β can increase the expression of MMPs by activating NF-kB. The excessive or inappropriate expression of MMP-9 may randomly and non-selectively destroy the extracellular matrix. TIMP-1 (tissue inhibitor of MMP-9) effects on ebb and flow of ECM by inhibiting activation of MMP-9...
February 7, 2018: Inflammation
Li Pan, Hongli Yang, Wenqiang Tang, Cong Xu, Shuangfeng Chen, Zhen Meng, Keyi Li, Haiying Chen
Zinc-finger protein 750 (ZNF750) is the potential anti-cancer gene in oral squamous cell carcinoma (OSCC). The present study was to investigate the expression changes of ZNF750 in OSCC tissue and to reveal the induction of altered mRNA expression profiles caused by over-expressed ZNF750 in CAL-27 cell. The expression level of ZNF750 in tissue specimens from OSCC patients was detected by immunohistochemistry. Gene expression profiling was performed using Human Signal Transduction PathwayFinder RT 2 Profiler™ PCR Array...
January 2, 2018: Oncotarget
Katerina Leonova, Alfiya Safina, Elimelech Nesher, Poorva Sandlesh, Rachel Pratt, Catherine Burkhart, Brittany Lipchick, Ilya Gitlin, Costakis Frangou, Igor Koman, Jianmin Wang, Kirill Kirsanov, Marianna G Yakubovskaya, Andrei V Gudkov, Katerina Gurova
Cellular Responses to the loss of genomic stability are well-established, while how mammalian cells respond to chromatin destabilization is largely unknown. We previously found that DNA demethylation on p53-deficient background leads to transcription of repetitive heterochromatin elements, followed by an interferon response, a phenomenon we named TRAIN (Transcription of Repeats Activates INterferon). Here, we report that curaxin, an anticancer small molecule, destabilizing nucleosomes via disruption of histone/DNA interactions, also induces TRAIN...
February 5, 2018: ELife
Qiang Zhao, Ke Wu, Nannan Li, Zhengmei Li, Fenglin Jin
Myocardial infarction (MI) is a heart disease with high morbidity and mortality rates, thus it is critical to identify genes that serve roles during its pathogenesis. The objective of the present study was to identify potentially relevant genes during the progression of the disease. Blood samples from patients with MI and normal controls (n=3/group) were obtained, the RNA was extracted and cDNA libraries were established. RNA sequencing (RNA-seq) was performed on a HiSeq 2500 platform and fragments per kilobase of exon per million fragments mapped was utilized to calculate the gene expression value following preprocessing of the RNA-seq data...
February 2018: Experimental and Therapeutic Medicine
Paul Hadweh, Iro Chaitoglou, Maria Joao Gravato-Nobre, Petros Ligoxygakis, George Mosialos, Eudoxia Hatzivassiliou
The human cylindromatosis tumor suppressor (HsCyld) has attracted extensive attention due to its association with the development of multiple types of cancer. HsCyld encodes a deubiquitinating enzyme (HsCYLD) with a broad range of functions that include the regulation of several cell growth, differentiation and death pathways. HsCyld is an evolutionarily conserved gene. Homologs of HsCyld have been identified in simple model organisms such as Drosophila melanogaster and Caenorhabditis elegans (C. elegans) which offer extensive possibilities for functional analyses...
2018: PloS One
Rumei Li, Qiwei Shen, Nan Wu, Min He, Naijia Liu, Jinya Huang, Bin Lu, Qiyuan Yao, Yehong Yang, Renming Hu
PURPOSE: To explore the relationship between miR-145 and ADP ribosylation factor 6 (Arf6) in regulating macrophage-mediated inflammation. METHODS: THP-1 cells were induced by 160 nM of phorbol 12-myristate 13-acetate (PMA) for 48 h to differentiate to macrophages and then were treated with LPS (100 ng/ml) for 8 h to simulate chronic metabolic inflammation in vitro. Dual-luciferase reporter assay was performed. MiR-145 siRNA and LV-ARF6-RNAi were used to up or down regulate miR-145 and Arf6 expression in THP-1 cells, respectively...
January 31, 2018: Endocrine
Hyunju Kim, Minsu Jang, Rackhyun Park, Daum Jo, Inho Choi, Joonho Choe, Won Keun Oh, Junsoo Park
Conessine, a steroidal alkaloid, is a potent histamine H3 antagonist with anti-malarial activity. We recently reported that conessine treatment interferes with H₂O₂-induced cell death by regulating autophagy. However, the cellular signaling pathways involved in conessine treatment are not fully understood. Here, we report that conessine reduces muscle atrophy by interfering with the expression of atrophy-related ubiquitin ligases MuRF-1 and atrogin-1. Promoter reporter assay revealed that conessine treatment inhibits FoxO3a-dependent transcription, NF-kappaB-dependent transcription and p53-dependent transcription...
February 1, 2018: Journal of Microbiology and Biotechnology
Zhiliang Lu, Zhaoli Chen, Yuan Li, Jingnan Wang, Zhirong Zhang, Yun Che, Jianbing Huang, Shouguo Sun, Shuangshuang Mao, Yuanyuan Lei, Yibo Gao, Jie He
The transforming growth factor β (TGF-β) signaling pathway plays anti- and pro-tumoral roles in the vast majority of cancers, and long noncoding RNAs have been reported to play key roles in the highly contextual response process. However, the roles of long noncoding RNAs (lncRNAs) in TGF-β signaling in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we performed RNA-seq to compare lncRNAs expression levels between TGF-β1-treated and untreated ESCC cells and observed that NF-kappaB-interacting lncRNA (NKILA) was remarkably upregulated by the classical TGF-β signaling pathway...
January 29, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Nadine Gehrke, Nadine Hövelmeyer, Ari Waisman, Beate K Straub, Julia Weinmann-Menke, Marcus A Wörns, Peter R Galle, Jörn M Schattenberg
BACKGROUND & AIMS: Interleukin (IL)-1-type cytokines including IL-1alpha, IL-1beta and interleukin-1 receptor antagonist (IL-1Ra) are among the most potent molecules of the innate immune system and exert biological activities through the ubiquitously expressed interleukin-1 receptor type 1 (IL-1RI). The role of IL-1RI in hepatocytes during acute liver failure (ALF) remains undetermined. METHODS: IL-1RI during ALF was investigated using a novel transgenic mouse model exhibiting deletion of all signaling-capable IL-1R isoforms in hepatocytes (IL-1RIHep-/-)...
January 20, 2018: Journal of Hepatology
Sascha Kopp, Jayashree Sahana, Tawhidul Islam, Asbjørn Graver Petersen, Johann Bauer, Thomas J Corydon, Herbert Schulz, Kathrin Saar, Norbert Huebner, Lasse Slumstrup, Stefan Riwaldt, Markus Wehland, Manfred Infanger, Ronald Luetzenberg, Daniela Grimm
Human MCF-7 breast cancer cells were exposed to a Random Positioning Machine (RPM). After 24 hours (h) the cells grew either adherently within a monolayer (AD) or within multicellular spheroids (MCS). AD and MCS populations were separately harvested, their cellular differences were determined performing qPCR on genes, which were differently expressed in AD and MCS cells. Gene array technology was applied to detect RPM-sensitive genes in MCF-7 cells after 24 h. Furthermore, the capability to form multicellular spheroids in vitro was compared with the intracellular distribution of NF-kappaB (NFκB) p65...
January 17, 2018: Scientific Reports
Elena Mata, Antonio Díaz-López, Ana M Martín-Moreno, Margarita Sánchez-Beato, Ignacio Varela, María J Mestre, Carlos Santonja, Fernando Burgos, Javier Menárguez, Mónica Estévez, Mariano Provencio, Beatriz Sánchez-Espiridión, Eva Díaz, Carlos Montalbán, Miguel A Piris, Juan F García
Defining the mutational landscape of classic Hodgkin lymphoma is still a major research goal. New targeted next-generation sequencing (NGS) techniques may identify pathogenic mechanisms and new therapeutic opportunities related to this disease. We describe the mutational profile of a series of 57 cHL cases, enriched in Hodgkin and Reed-Sternberg (HRS) cells. Overall, the results confirm the presence of strong genomic heterogeneity. However, several variants were consistently detected in genes related to relevant signaling pathways, such as GM-CSF/IL-3, CBP/EP300, JAK/STAT, NF-kappaB, and numerous variants of genes affecting the B-cell receptor (BCR) pathway, such as BTK, CARD11, BCL10, among others...
December 19, 2017: Oncotarget
Bruno R B Pires, Rafael C M C Silva, Gerson M Ferreira, Eliana Abdelhay
Nuclear Factor-kappa B (NF-κB) is a transcription factor family that regulates a large number of genes that are involved in important physiological processes, including survival, inflammation, and immune responses. More recently, constitutive expression of NF-κB has been associated with several types of cancer. In addition, microorganisms, such as viruses and bacteria, cooperate in the activation of NF-κB in tumors, confirming the multifactorial role of this transcription factor as a cancer driver. Recent reports have shown that the NF-κB signaling pathway should receive attention for the development of therapies...
January 9, 2018: Genes
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