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https://www.readbyqxmd.com/read/29679570/hmgb1-containing-nucleosome-mediates-chemotherapy-induced-metastasis-of-human-lung-cancer
#1
Kailing Wang, Shan Shan, Shenqi Wang, Xiaohua Gu, Xiaohui Zhou, Tao Ren
While chemotherapy is an important and widely used therapeutic for cancer, it may facilitate cancer metastasis. Herein, we report that human lung cancer cells exerted higher invasion and metastasis after chemotherapy. In a human lung cancer xenograft model, chemotherapy promotes the cancer invasion and metastasis in HMGB1-dependent manner. Further studies identify HMGB1-containing nucleosome from chemotherapy-induced apoptotic cancer cells as an effective factor. Such nucleosome functions through TLR4 and TLR9 to drive cancer invasion and metastasis...
April 18, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29679017/nf%C3%AE%C2%BAb-activation-in-differentiating-glioblastoma-stem-like-cells-is-promoted-by-hyaluronic-acid-signaling-through-tlr4
#2
Eva Ferrandez, Olga Gutierrez, David San Segundo, Jose L Fernandez-Luna
We have previously described that the NFκB pathway is upregulated during differentiation of glioblastoma stem-like cells (GSCs) which keeps differentiating GSCs in a proliferative astrocytic precursor state. However, extracellular signals and cellular mediators of this pathway are not clear yet. Here, we show that TLR4 is a key factor to promote NFκB activation in differentiating GSCs. TLR4 is upregulated during differentiation of GSCs and promotes transcriptional activation of NFκB as determined by luciferase-reporter assays and expression of NFκB target genes...
April 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29678610/nrf2-protects-against-acute-lung-injury-and-inflammation-by-modulating-tlr4-and-akt-signaling
#3
Jia Yan, Jingjie Li, Lei Zhang, Yu Sun, Jue Jiang, Yan Huang, Hui Xu, Hong Jiang, Rong Hu
Lung injury, which is associated with systemic inflammatory responses, is a common problem with significant morbidity and mortality. Here, we examined the involvement of toll-like receptor 4 (TLR4) and nuclear factor erythroid 2-related factor 2 (Nrf2) on intestinal ischemia-reperfusion (I/R)-induced lung injury in vivo and in vitro. Analysis of lung tissues in Nrf2-knockout mice by western blotting, immunohistochemistry, and TUNEL assay, and analysis of bronchoalveolar lavage fluid showed that Nrf2 deficiency upregulated TLR4, enhanced I/R-induced lung injury, apoptosis, inflammation, and autophagy, and increased the I/R-induced inactivation of Akt...
April 17, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29678225/synergistic-effect-of-co-stimulation-of-membrane-and-endosomal-tlrs-on-chicken-innate-immune-responses
#4
Sungwon Kim, Pete Kaiser, Dominika Borowska, Lonneke Vervelde
Toll-like receptor (TLR) ligands (TLR-Ls) are critical activators of immunity and are successfully being developed as vaccine adjuvants in both mammals and birds. In this study, we investigated the synergistic effect of co-stimulation of membrane and endosomal TLRs on the innate immune responses using chicken bone marrow-derived macrophages (BMMs), and studied the effect of age on the induction of innate responses. BMMs from 1 and 4-week-old birds were stimulated with Pam3Cys-SK4 (PCSK; TLR2), synthetic monophosphoryl lipid A (MPLA), Di[3-deoxy-d-manno-octulosonyl]-lipid A ammonium salt (KLA; TLR4), Gardiquimod, Resiquimod (R848; TLR7), CpG class B and C (TLR21)...
May 2018: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29678206/biliverdin-reductase-a-attenuated-gmh-induced-inflammatory-response-in-the-spleen-by-inhibiting-toll-like-receptor-4-through-enos-no-pathway
#5
Yiting Zhang, Yan Ding, Tai Lu, Yixin Zhang, Ningbo Xu, Devin W McBride, Jiping Tang, John H Zhang
BACKGROUND: Germinal matrix hemorrhage (GMH) is a common neurologic event with high morbidity and mortality in preterm infants. Spleen has been reported to play a critical role in inflammatory responses by regulating peripheral immune cells which contributes to secondary brain injury. METHODS: The current study investigated the mechanistic role of biliverdin reductase-A (BLVRA) in the splenic response and brain damage in neonates following a collagenase GMH model...
April 20, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29676954/genome-wide-association-study-identifies-loci-and-candidate-genes-for-internal-organ-weights-in-simmental-beef-cattle
#6
Bingxing An, Jiangwei Xia, Tianpeng Chang, Xiaoqiao Wang, Jian Miao, Lingyang Xu, Lupei Zhang, Xue Gao, Yan Chen, Junya Li, Huijiang Gao
Cattle internal organs as accessible raw materials have a long history of being widely used in beef processing, feed and pharmaceutical industry. These traits not only are of economic interest to breeders, but they are intrinsically linked to many valuable traits, such as growth, health, and productivity. Using the Illumina Bovine HD 770K SNP array, we performed a genome-wide association study for heart weight (HW), liver weight (LIW), spleen weight (SW), lung weight (LUW) and kidney weight (KW) in 1217 Simmental cattle...
April 20, 2018: Physiological Genomics
https://www.readbyqxmd.com/read/29676511/role-of-the-high-mobility-group-box-1-signalling-axes-via-the-receptor-for-advanced-glycation-end-products-and-toll-like-receptor-4-in-the-immunopathology-of-oral-lichen-planus-a-potential-drug-target
#7
Abdelhakim Salem, Rabeia Almahmoudi, Mari Vehviläinen, Tuula Salo
High mobility group box 1 (HMGB1) is an extremely conserved DNA-binding protein that stabilizes nucleosomes and facilitates gene transcription in mammalian cells. When released extracellularly, HMGB1 becomes an alarmin that can mediate systemic diseases. High mobility group box 1 signals via two main receptors: receptor for advanced glycation end-products (RAGE) and toll-like receptor-4 (TLR4). We hypothesized that HMGB1 expression is increased in patients with oral lichen planus (OLP) relative to healthy controls...
April 20, 2018: European Journal of Oral Sciences
https://www.readbyqxmd.com/read/29676074/immune-characterization-of-bone-marrow-derived-models-of-mucosal-and-connective-tissue-mast-cells
#8
Sara Benedé, Evan Cody, Charuta Agashe, M Cecilia Berin
PURPOSE: It is well appreciated that mast cells (MCs) demonstrate tissue-specific imprinting, with different biochemical and functional properties between connective tissue MCs (CTMCs) and mucosal MCs (MMCs). Although in vitro systems have been developed to model these different subsets, there has been limited investigation into the functional characteristics of the 2 major MC subsets. Here, we report the immunologic characterization of 2 MCs subsets developed in vitro from bone marrow progenitors modeling MMCs and CTMCs...
May 2018: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/29675728/histone-deacetylase-2-inhibitor-cay10683-alleviates-lipopolysaccharide-induced-neuroinflammation-through-attenuating-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway
#9
Fang-Zhou Jiao, Yao Wang, Hai-Yue Zhang, Wen-Bin Zhang, Lu-Wen Wang, Zuo-Jiong Gong
Neuroinflammation involves in the progression of many central nervous system diseases. Several studies have shown that histone deacetylase (HDAC) inhibitors modulated inflammatory responses in lipopolysaccharide (LPS) stimulated microglia. While, the mechanism is still unclear. The aim of present study was to investigate the effect of HDAC2 inhibitor CAY10683 on inflammatory responses and TLR4/NF-κB signaling pathways in LPS activated BV2 microglial cells and LPS induced mice neuroinflammation. The effect of CAY10683 on cell viability of BV2 microglial cells was detected by CCK-8 assay...
April 19, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29675369/boxb-mediate-balb-c-mice-corneal-inflammation-through-a-tlr4-myd88-dependent-signaling-pathway-in-aspergillus-fumigatus-keratitis
#10
Min Liu, Cui Li, Gui-Qiu Zhao, Jing Lin, Cheng-Ye Che, Qiang Xu, Qian Wang, Rui Xu, Ya-Wen Niu
AIM: To investigate whether high-mobility group box 1 (HMGB1) Boxb exacerbates BALB/c mice corneal immune responses and inflammatory through the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)-dependent signaling pathway in Aspergillus fumigatus ( A. fumigatus ) keratitis. METHODS: The mice corneas were pretreated with phosphate buffer saline (PBS), Boxb before A. fumigatus infection. The abdominal cavity extracted macrophages were pretreated with PBS, Boxb, TLR4 inhibitor (CLI-095), Dimethyl sulfoxide (DMSO) separately before A...
2018: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/29675024/activation-of-the-absent-in-melanoma-2-inflammasome-in-peripheral-blood-mononuclear-cells-from-idiopathic-pulmonary-fibrosis-patients-leads-to-the-release-of-pro-fibrotic-mediators
#11
Michela Terlizzi, Antonio Molino, Chiara Colarusso, Chantal Donovan, Pasquale Imitazione, Pasquale Somma, Rita P Aquino, Philip M Hansbro, Aldo Pinto, Rosalinda Sorrentino
Idiopathic pulmonary fibrosis (IPF) is a chronic fibro-proliferative disease characterized by poor prognosis, with a mean survival of ~2-3 years after definite diagnosis. The cause of IPF is still unknown but it is a heterogeneous condition in which the aberrant deposition of extracellular matrix leads to extensive lung remodeling. This remodeling is a consequence of inflammatory responses, but the mechanisms involved are poorly understood. In this study, we first analyzed a bleomycin-induced mouse model, which showed that higher expression of IL-1β, but not IL-18, was correlated to pulmonary cell infiltration and fibrosis...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29673358/contribution-of-tlr4-signaling-in-intermittent-hypoxia-mediated-atherosclerosis-progression
#12
Xianqin Zeng, Rong Guo, Mei Dong, Julia Zheng, Huili Lin, Huixia Lu
BACKGROUND: Intermittent hypoxia (IH), a typical character of obstructive sleep apnea (OSA), is related to atherogenesis. However, the role of IH on atherosclerosis (AS) progression and the mechanisms involved remains poorly understood. METHODS: In the present study, high-fat fed ApoE-/- mice were treated with recombinant shRNA-TLR4 lentivirus and exposed to IH. Atherosclerotic lesions on the en face aorta and cross-sections of aortic root were examined by Oil-Red O staining...
April 19, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29673286/inhibition-of-autophagy-with-3-methyladenine-is-protective-in-a-lethal-model-of-murine-endotoxemia-and-polymicrobial-sepsis
#13
Qirui Li, Lingyun Li, Xiaoyuan Fei, Yuanyue Zhang, Chang Qi, Shuyao Hua, Feili Gong, Min Fang
Here, the regulatory role of autophagy is examined in both an LPS-induced lethal endotoxic shock mouse model and cecal ligation and puncture (CLP) mouse model. Autophagy-inhibitor 3-methyladenine (3-MA) and autophagy-enhancer rapamycin were administrated to mice challenged with LPS or CLP. Animals challenged with LPS or CLP combined with 3-MA displayed increased survival after endotoxemia, but LPS combined with rapamycin worsened the endotoxic shock of the mice. Among the different organs studied, the lungs and intestines exhibited significant differences among LPS alone, LPS combined with 3-MA and LPS combined with rapamycin...
January 1, 2018: Innate Immunity
https://www.readbyqxmd.com/read/29673285/tlr-agonist-combinations-that-stimulate-th-type-i-polarizing-responses-from-human-neonates
#14
Naveen Surendran, Andrea Simmons, Michael E Pichichero
Each year millions of neonates die due to vaccine preventable infectious diseases. Our study seeks to develop novel neonatal vaccines and improve immunogenicity of early childhood vaccines by incorporating TLR agonist-adjuvant combinations that overcome the inherent neonatal Th2 bias and stimulate Th1 polarizing response from neonatal APCs. We systematically stimulated cord blood mononuclear cells with single and multiple combinations of TLR agonists and measured levels of IL-12p70, IFN-γ, IFN-α, IL-10, IL-13, TNF-α, IL-6 and IL-1β from cell culture supernatants...
January 1, 2018: Innate Immunity
https://www.readbyqxmd.com/read/29673059/the-tlr4-ire1%C3%AE-pathway-activation-contributes-to-palmitate-elicited-lipotoxicity-in-hepatocytes
#15
Chen Shen, Wang Ma, Lei Ding, Songtao Li, Xiaobing Dou, Zhenyuan Song
Lipotoxicity induced by saturated fatty acids (SFAs) plays a pathological role in the development of non-alcoholic fatty liver disease (NAFLD); however, the exact mechanism(s) remain to be clearly elucidated. Toll-like receptor (TLR) 4 plays a fundamental role in activating the innate immune system. Intriguingly, hepatocytes express TLR4 and machinery for TLR4 signalling pathway. That liver-specific TLR4 knockout mice are protective against diet-induced NAFLD suggests that hepatocyte TLR4 signalling pathway plays an important role in NAFLD pathogenesis...
April 19, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29671417/cyanidin-attenuates-a%C3%AE-25-35-induced-neuroinflammation-by-suppressing-nf-%C3%AE%C2%BAb-activity-downstream-of-tlr4-nox4-in-human-neuroblastoma-cells
#16
Sarinthorn Thummayot, Chainarong Tocharus, Pichaya Jumnongprakhon, Apichart Suksamrarn, Jiraporn Tocharus
Cyanidin is polyphenolic pigment found in plants. We have previously demonstrated that cyanidin protects nerve cells against Aβ25-35 -induced toxicity by decreasing oxidative stress and attenuating apoptosis mediated by both the mitochondrial apoptotic pathway and the ER stress pathway. To further elucidate the molecular mechanisms underlying the neuroprotective effects of cyanidin, we investigated the effects of cyanidin on neuroinflammation mediated by the TLR4/NOX4 pathway in Aβ25-35 -treated human neuroblastoma cell line (SK-N-SH)...
April 19, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29670923/cathelicidin-ll-37-affects-surface-and-intracellular-toll-like-receptor-expression-in-tissue-mast-cells
#17
Justyna Agier, Ewa Brzezińska-Błaszczyk, Paulina Żelechowska, Magdalena Wiktorska, Jacek Pietrzak, Sylwia Różalska
Undoubtedly, mast cells take part in host defense against microorganisms as they are numerous at the portal of infection, they release many proinflammatory and antimicrobial mediators, and they express pattern recognition receptors, such as TLRs. These receptors play a key role in recognition and binding molecules associated with microorganisms and molecules associated with damage. Cathelicidins exhibit direct antimicrobial activities against a broad spectrum of microbes by perturbing their cell membranes. Accumulating evidence suggests a role for these molecules in supporting cell activation...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29670922/clinicopathological-features-and-increased-expression-of-toll-like-receptor-4-of-gastric-cardia-cancer-in-a-high-risk-chinese-population
#18
Guangcan Chen, Muming Xu, Jingyao Chen, Liangli Hong, Wenting Lin, Shukun Zhao, Guohong Zhang, Guo Dan, Shuhui Liu
The incidence of gastric cardia cancer (GCC) is high in China. However, the clinicopathological characteristics and the carcinogenesis of GCC are unclear. Toll-like receptor 4 (TLR4) is an important innate immunity receptor and has a role in non-GCC (NGCC). We compared the clinicopathological characteristics of GCC patients from a high-risk area in China to esophageal cancer (EC) patients. Immunohistochemistry for TLR4 was performed in 201 histological samples of normal gastric cardia mucosa ( n = 11), gastric cardia inflammation ( n = 87), and GCC ( n = 103)...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29670828/high-expression-of-the-hmgb1-tlr4-axis-and-its-downstream-signaling-factors-in-patients-with-parkinson-s-disease-and-the-relationship-of-pathological-staging
#19
Yi Yang, Chenyang Han, Li Guo, Qiaobin Guan
Objective: To detect the expression of high-mobility group box protein 1 (HMGB1) and toll-like receptor 4 (TLR4) and their downstream signaling factors-myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF-κB), and tumor necrosis factor alpha (TNF-α)-in the sera of patients with Parkinson's disease (PD) in order to evaluate the relationship of the HMGB1-TLR4 axis with PD development and progression. Methods: The serum HMGB1 and TLR4 protein levels of 120 patients with PD and 100 healthy volunteers were measured using double-antibody sandwich ELISA, and their correlations with PD staging, disease duration, drug treatment effectiveness, and clinical classification were analyzed...
April 2018: Brain and Behavior
https://www.readbyqxmd.com/read/29670526/taraxasterol-inhibits-lps-induced-inflammatory-response-in-bv2-microglia-cells-by-activating-lxr%C3%AE
#20
Bin Liu, Zhaoqi He, Jingjing Wang, Zhuoyuan Xin, Jiaxin Wang, Fan Li, Yunhe Fu
Neuroinflammation plays a critical role in the development of neurodegenerative diseases. Taraxasterol, a pentacyclic-triterpene isolated from Taraxacum officinale , has been reported to have anti-inflammatory effect. The aim of this study was to investigate the anti-inflammatory effects and mechanism of taraxasterol in LPS-stimulated BV2 microglia cells. BV2 microglia cells were treated with taraxasterol 12 h before LPS stimulation. The effects of taraxasterol on LPS-induced TNF-α and IL-1β production were detected by ELISA...
2018: Frontiers in Pharmacology
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