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https://www.readbyqxmd.com/read/28725984/cytokine-expression-and-barrier-disruption-in-human-corneal-epithelial-cells-induced-by-alarmin-released-from-necrotic-cells
#1
Ken Fukuda, Waka Ishida, Yusaku Miura, Tatsuma Kishimoto, Atsuki Fukushima
PURPOSE: Dying cells release endogenous molecules known as alarmins that signal danger to surrounding tissue. We investigated the effects of necrotic cell-derived alarmins on cytokine expression and barrier function in human corneal epithelial cells. METHODS: The release of interleukin (IL)-6 and IL-8 from immortalized human corneal epithelial (HCE) cells in culture was measured with enzyme-linked immunosorbent assays. The abundance of IL-6 and 8 mRNAs was quantitated by reverse transcription and real-time polymerase chain reaction analysis...
July 19, 2017: Japanese Journal of Ophthalmology
https://www.readbyqxmd.com/read/28723651/suppression-of-clc-3-chloride-channel-reduces-the-aggressiveness-of-glioma-through-inhibiting-nuclear-factor-%C3%AE%C2%BAb-pathway
#2
Bing Wang, Jing Xie, Hai-Yong He, En-Wen Huang, Qing-Hua Cao, Lun Luo, Yong-Shi Liao, Ying Guo
CLC-3 chloride channel plays important roles on cell volume regulation, proliferation and migration in normal and cancer cells. Recent growing evidence supports a critical role of CLC-3 in glioma metastasis, however, the mechanism underlying is unclear. This study finds that CLC-3 is upregulated in glioma tissues and positively correlated with WHO histological grade. Patients with high CLC-3 expression had an overall shorter survival time, whereas patients with low expression of CLC-3 had a better survival time...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723419/nf-%C3%AE%C2%BAb-p65-serine-467-phosphorylation-sensitizes-mice-to-weight-gain-and-tnf%C3%AE-or-diet-induced-inflammation
#3
Tabea Riedlinger, Marleen B Dommerholt, Tobias Wijshake, Janine K Kruit, Nicolette Huijkman, Daphne Dekker, Mirjam Koster, Niels Kloosterhuis, Debby P Y Koonen, Alain de Bruin, Darren Baker, Marten H Hofker, Jan van Deursen, Johan W Jonker, M Lienhard Schmitz, Bart van de Sluis
The NF-κB family of transcription factors is essential for an effective immune response, but also controls cell metabolism, proliferation and apoptosis. Its broad relevance and the high connectivity to diverse signaling pathways require a tight control of NF-κB activity. To investigate the control of NF-κB activity by phosphorylation of the NF-κB p65 subunit, we generated a knock-in mouse model in which serine 467 (the mouse homolog of human p65 serine 468) was replaced with a non-phosphorylatable alanine (S467A)...
July 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28714847/modulation-of-the-transcription-factor-nf-%C3%AE%C2%BAb-in-antigen-presenting-cells-by-bovine-respiratory-syncytial-virus-small-hydrophobic-protein
#4
Nicola Pollock, Geraldine Taylor, Fatoumatta Jobe, Efrain Guzman
Bovine respiratory syncytial virus (BRSV) is an important cause of respiratory disease in young cattle and is closely related to human RSV (HRSV), which causes severe respiratory disease in infants and the elderly. The RSV genome encodes a small hydrophobic (SH) protein with viroporin activity. Previous studies have shown that recombinant BRSV lacking the SH gene (rBRSVΔSH) is attenuated in the lungs, but not in the upper respiratory tract, of calves and mucosal vaccination with rBRSVΔSH induced long-lasting protective immunity...
July 17, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28713342/nf-%C3%AE%C2%BAbp50-and-hdac1-interaction-is-implicated-in-the-host-tolerance-to-infection-mediated-by-the-bacterial-quorum-sensing-signal-2-aminoacetophenone
#5
Arunava Bandyopadhaya, Amy Tsurumi, Laurence G Rahme
Some bacterial quorum sensing (QS) small molecules are important mediators of inter-kingdom signaling and impact host immunity. The QS regulated small volatile molecule 2-aminoacetophenone (2-AA), which has been proposed as a biomarker of Pseudomonas aeruginosa colonization in chronically infected human tissues, is critically involved in "host tolerance training" that involves a distinct molecular mechanism of host chromatin regulation through histone deacetylase (HDAC)1. 2-AA's epigenetic reprogramming action enables host tolerance to high bacterial burden and permits long-term presence of P...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28706958/toll-like-receptor-2-mediated-nf-kappa-b-pathway-activation-in-ocular-surface-epithelial-cells
#6
Aihua Hou, Min Qi Tin, Louis Tong
BACKGROUND: Gram-positive bacteria stimulate Toll-like receptor (TLR) 2 and then activate the pro-inflammatory nuclear factor-kappa B (NF-κB) pathway. As the human ocular surface is heavily colonised by gram-positive cocci bacteria, a balance of activation/repression of NF-κB target genes is essential to avoid uncontrolled infection or autoimmune-related inflammation. It is advantageous to test NF-κB targeting molecules in an ocular surface culture system that allows assessment of temporal NF-κB activation in a longitudinal fashion without destruction of cells...
2017: Eye and Vision (London, England)
https://www.readbyqxmd.com/read/28706459/beauvericin-a-cyclic-peptide-inhibits-inflammatory-responses-in-macrophages-by-inhibiting-the-nf-%C3%AE%C2%BAb-pathway
#7
Sulgi Yoo, Mi-Yeon Kim, Jae Youl Cho
Beauvericin (BEA), a cyclic hexadepsipeptide produced by the fungus Beauveria bassiana, is known to have anti-cancer, anti-inflammatory, and anti-microbial actions. However, how BEA suppresses macrophage-induced inflammatory responses has not been fully elucidated. In this study, we explored the anti-inflammatory properties of BEA and the underlying molecular mechanisms using lipopolysaccharide (LPS)-treated macrophage-like RAW264.7 cells. Levels of nitric oxide (NO), mRNA levels of transcription factors and the inflammatory genes inducible NO synthase (iNOS) and interleukin (IL)-1, and protein levels of activated intracellular signaling molecules were determined by Griess assay, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), luciferase reporter gene assay, and immunoblotting analysis...
July 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28706417/indole-phytoalexin-derivatives-induce-mitochondrial-mediated-apoptosis-in-human-colorectal-carcinoma-cells
#8
Viera Tischlerova, Martin Kello, Mariana Budovska, Jan Mojzis
AIM: To investigate the mechanism of the antiproliferative effect of synthetic indole phytoalexin derivatives on human colorectal cancer cell lines. METHODS: Changes in cell proliferation and the cytotoxic effect of the tested compounds on human colorectal cancer cell lines and human fibroblasts were evaluated using MTS and BrdU assay, allowing us to choose the most potent substance. Cell cycle alterations were analyzed using flow cytometric analysis. The apoptosis-inducing effect of compound K-453 on the HCT116 cell line was examined with annexin V/PI double staining using flow cytometry, as well as acridine orange/propidium iodide (AO/PI) staining...
June 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28704656/induction-of-inkit-by-viral-infection-negatively-regulates-antiviral-responses-through-inhibiting-phosphorylation-of-p65-and-irf3
#9
Bin Lu, Yujie Ren, Xueqin Sun, Cuijuan Han, Hongyan Wang, Yuxuan Chen, Qianqian Peng, Yongbo Cheng, Xiaoliang Cheng, Qiyun Zhu, Wenxin Li, Hong-Liang Li, Hai-Ning Du, Bo Zhong, Zan Huang
The transcription factors p65 and IRF3 play key roles in the induction of cellular antiviral responses. Phosphorylation of p65 and IRF3 is required for their activity and constitutes a key checkpoint. Here we report that viral infection induced upregulation of INKIT, an inhibitor for NF-κB and IRF3 that restricted innate antiviral responses by blocking phosphorylation of p65 and IRF3. INKIT overexpression inhibited virus-induced phosphorylation of p65 and IRF3 and expression of downstream genes. In contrast, knockdown or knockout of INKIT had the opposite effect: Inkit(-/-) mice produced elevated levels of type I interferons and proinflammatory cytokines and were more resistant to lethal viral infection compared to wild-type...
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28696292/acute-inflammation-regulates-neuroregeneration-through-the-nf-%C3%AE%C2%BAb-pathway-in-olfactory-epithelium
#10
Mengfei Chen, Randall R Reed, Andrew P Lane
Adult neural stem cells/progenitor cells residing in the basal layer of the olfactory epithelium are capable of reconstituting the neuroepithelium even after severe damage. The molecular events underlying this regenerative capacity remain elusive. Here we show that the repair of neuroepithelium after lesioning is accompanied by an acute, but self-limited, inflammatory process. Attenuation of inflammatory cell recruitment and cytokine production by dexamethasone impairs proliferation of progenitor horizontal basal cells (HBCs) and subsequent neuronal differentiation...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28693920/s100b-promotes-injury-induced-vascular-remodeling-through-modulating-smooth-muscle-phenotype
#11
Teng Cao, Lei Zhang, Ling-Ling Yao, Fei Zheng, Lu Wang, Jian-Ye Yang, Ling-Yun Guo, Xing-Yuan Li, Yu-Wen Yan, Ya-Mu Pan, Miao Jiang, Long Chen, Jun-Ming Tang, Shi-You Chen, Jia-NingWang
S100B is a biomarker of nervous system injury, but it is unknown if it is also involved in vascular injury. In the present study, we investigated S100B function in vascular remodeling following injury. Balloon injury in rat carotid artery progressively induced neointima formation while increasing S100B expression in both neointimal vascular smooth muscle (VSMC) and serum along with an induction of proliferating cell nuclear antigen (PCNA). Knockdown of S100B by its shRNA delivered by adenoviral transduction attenuated the PCNA expression and neointimal hyperplasia in vivo and suppressed PDGF-BB-induced VSMC proliferation and migration in vitro...
July 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28690191/methyl-e-3-3-4-dihydroxyphenyl-acryloyl-tryptophanate-can-suppress-mcp-1-expression-by-inhibiting-p38-map-kinase-and-nf-%C3%AE%C2%BAb-in-lps-stimulated-differentiated-thp-1-cells
#12
Jae B Park, Thomas T Y Wang
Methyl (E)-(3-(3,4-dihydroxyphenyl)acryloyl)tryptophanate (MHAT) is an O-methyl ester of javamide-II showing strong anti-inflammatory activity. Therefore, in this study, MHAT was chemically synthesized, and its effects on p38 MAP kinase, NF-κB, and monocyte chemotactic factor-1 (MCP-1) expression were investigated in LPS-stimulated differentiated THP-1 cells. MHAT inhibited p38 MAP kinase with an IC50 of 12μM, and the inhibition was supported by an in silico model showing that its binding to p38 MAP kinase was stronger than that of SB203580...
July 6, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28690034/interplay-of-inflammatory-gene-expression-in-pericytes-following-japanese-encephalitis-virus-infection
#13
Cheng-Yi Chang, Jian-Ri Li, Yen-Chuan Ou, Shih-Yi Lin, Ya-Yu Wang, Wen-Ying Chen, Yu-Hui Hu, Ching-Yi Lai, Chen-Jung Chang, Chun-Jung Chen
Neuroinflammation is a pathological hallmark and has been implicated in the pathogenesis of Japanese encephalitis. Although brain pericytes show regulatory effects on neuroinflammation, their involvement in Japanese encephalitis-associated neuroinflammation is not understood. Here, we demonstrated that brain microvascular pericytes could be an alternative cellular source for the induction and/or amplification of neuroinflammation caused by Japanese encephalitis virus (JEV) infection. Infection of cultured pericytes with JEV caused profound production of IL-6, RANTES, and prostaglandin E2 (PGE2)...
July 6, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28687535/endothelial-nf-%C3%AE%C2%BAb-blockade-abrogates-anca-induced-gn
#14
Mira Choi, Adrian Schreiber, Claudia Eulenberg-Gustavus, Claus Scheidereit, Jan Kamps, Ralph Kettritz
ANCA-associated vasculitis (AAV) is a highly inflammatory condition in which ANCA-activated neutrophils interact with the endothelium, resulting in necrotizing vasculitis. We tested the hypothesis that endothelial NF-κB mediates necrotizing crescentic GN (NCGN) and provides a specific treatment target. Reanalysis of kidneys from previously examined murine NCGN disease models revealed NF-κB activation in affected kidneys, mostly as a p50/p65 heterodimer, and increased renal expression of NF-κB-dependent tumor necrosis factor α (TNF-α)...
July 7, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28687276/nap1l1-regulates-nf-%C3%AE%C2%BAb-signaling-pathway-acting-on-anti-apoptotic-mcl-1-gene-expression
#15
Toshiaki Tanaka, Yasukazu Hozumi, Mitsuyoshi Iino, Kaoru Goto
Nuclear factor-κB (NF-κB) participates in apoptosis signaling pathway under various pathophysiological conditions. It exerts transcriptional control on the anti-apoptotic Bcl-2 family, such as Bcl-2, Bcl-xl, and Mcl-1, which act on the mitochondrial outer membrane. Previously, we described that NF-κB is negatively regulated by diacylglycerol kinase ζ (DGKζ), an enzyme that phosphorylates a lipid second messenger diacylglycerol. DGKζ downregulation enhances inhibitors of NF-κB α (IκBα) degradation and p65 subunit phosphorylation, leading to enhanced NF-κB transcriptional activity...
July 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28685413/telluric-acid-ameliorates-endotoxemic-kidney-injury-in-mice-involvement-of-tlr4-nrf2-and-pi3k-akt-signaling-pathways
#16
Ahmed F Mohamed, Marwa M Safar, Hala F Zaki, Helmy M Sayed
Being one of the most abundant trace elements in the human body, the therapeutic potential of tellurium-based compounds has been a target of interest. Recent reports denoted their redox-modulating and anti-inflammatory activities in experimental endotoxemia. However, their potential nephroprotective effect against endotoxemic kidney injury is yet to be elucidated. This study investigated the possible renoprotective effect of telluric acid (TEL) against lipopolysaccharide (LPS)-induced acute kidney injury (AKI) in mice, targeting toll-like receptor 4 (TLR4), phosphoinositide 3-kinase (PI3K)/Akt, and nuclear factor-erythroid 2-related factor-2 (Nrf2) pathways as possible mechanistic contributors to TEL's effect...
July 6, 2017: Inflammation
https://www.readbyqxmd.com/read/28681591/o-glcnacylation-of-nf-kappab-promotes-lung-metastasis-of-cervical-cancer-cells-via-upregulation-of-cxcr4-expression
#17
Akhtar Ali, Sung Hwan Kim, Min Jun Kim, Mee Young Choi, Sang Soo Kang, Gyeong Jae Cho, Yoon Sook Kim, Jun-Young Choi, Wan Sung Choi
C-X-C chemokine receptor 4 (CXCR4) stimulates cancer metastasis. NF-kappaB regulates CXCR4 expression in cancer cells, and O-GlcNAc modification of NF-kappaB promotes its transcriptional activity. Here, we determined whether CXCR4 expression is affected by O-GlcNAcylation of NF-kappaB in lung metastasis of cervical cancer. We found elevated levels of O-linked-Nactylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-kappaB p65 (p65) and CXCR4 in cervical cancer cells...
July 6, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28681587/functional-characterization-of-the-promoter-of-carbonyl-reductase-1-gene-in-porcine-endometrial-cells
#18
Ai-Ling Zhang, Xian-Yue Sun, Qi Yin, Jian-Hua Zeng, Zhe Zhang, Jia-Qi Li, Hao Zhang
Prostaglandins (PGs) play a critical role in porcine reproduction, of which prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) exert antiluteolytic and luteolysis actions, respectively. As a rate-limiting enzyme, carbonyl reductase 1 (CBR1) catalyzes the conversion of PGE2 to PGF2α. A high ratio of PGE2:PGF2α is beneficial to the establishment and maintenance of porcine pregnancy. PG is essential for the establishment of pregnancy which resembles the proinflammatory response and nuclear factor κB (NF-κB) is involved in the process...
July 2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/28680569/ppar%C3%AE-attenuates-hypoxia-induced-hypertrophic-transcriptional-pathways-in-the-heart
#19
Abubakr Chaudhry, Kristal A Carthan, Bum-Yong Kang, John Calvert, Roy L Sutliff, C Michael Hart
Chronic hypoxia-induced pulmonary hypertension (PH) is characterized by increased pressure and resistance in the pulmonary vasculature and hypertrophy of the right ventricle (RV). The transcription factors, nuclear factor activated T-cells (NFAT), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB/p65) contribute to RV hypertrophy (RVH). Because peroxisome proliferator-activated receptor gamma (PPARγ) activation attenuates hypoxia-induced PH and RVH, we hypothesized that PPARγ inhibits activation of RV hypertrophic transcriptional signaling mechanisms...
March 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28674400/endotoxin-tolerance-in-mast-cells-its-consequences-for-ige-mediated-signalling-and-the-effects-of-bcl3-deficiency
#20
Magdalena Poplutz, Maryna Levikova, Juliane Lüscher-Firzlaff, Marina Lesina, Hana Algül, Bernhard Lüscher, Michael Huber
Stimulation with lipopolysaccharide (LPS; endotoxin) not only causes rapid production of proinflammatory cytokines, but also induces a state of LPS hypo-responsiveness to a second LPS stimulation (endotoxin tolerance (ET)). Murine bone marrow-derived MCs (BMMCs) and peritoneal MCs (PMCs) developed ET as shown by an abrogated production of Il6/Tnf RNAs and IL-6/TNF-α proteins. In naive BMMCs, LPS stimulation induced a transient decline in the trimethylation of lysine 9 of the core histone H3 (H3K9me3), a suppressive chromatin mark, at the Il6/Tnf promoters, which correlated with p50(NFκB) and p65(NFκB) binding...
July 3, 2017: Scientific Reports
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