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https://www.readbyqxmd.com/read/28056977/corilagin-ameliorates-the-extreme-inflammatory-status-in-sepsis-through-tlr4-signaling-pathways
#1
Hua-Rong Li, Jie Liu, Shu-Ling Zhang, Tao Luo, Fei Wu, Ji-Hua Dong, Yuan-Jin Guo, Lei Zhao
BACKGROUND: Sepsis is one of the serious disorders in clinical practice. Recent studies found toll-like receptors 4 (TLR4) played an important role in sepsis. In this study, we tried to find the influence of Corilagin on TLR4 signal pathways in vitro and in vivo. METHODS: The cellular and animal models of sepsis were established by LPS and then interfered with Corilagin. Real-time PCR and western blot were employed to detect the mRNA and protein expressions of TLR4, MyD88, TRIF and TRAF6...
January 5, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28052863/double-stranded-rna-up-regulates-the-expression-of-inflammatory-mediators-in-human-aortic-valve-cells-through-the-tlr3-trif-non-canonical-nf-%C3%AE%C2%BAb-pathway
#2
Qiong Zhan, Rui Song, Fei Li, Lihua Ao, Qingchun Zeng, Dingli Xu, David A Fullerton, Xianzhong Meng
BACKGROUND: Calcific aortic valve disease (CAVD) is a chronic inflammatory condition and the inflammatory responses of aortic valve interstitial cells (AVICs) play a critical role in the disease progression. Double-stranded RNA (dsRNA) released from damaged or stressed cells is pro-inflammatory and may contribute to the mechanism of chronic inflammation observed in diseased aortic valves. The objective of this study is to determine the effect of dsRNA on AVIC inflammatory responses and the underlying mechanism...
January 4, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28049762/the-tyrosine-kinase-src-promotes-phosphorylation-of-the-kinase-tbk1-to-facilitate-type-i-interferon-production-after-viral-infection
#3
Xuelian Li, Mingjin Yang, Zhou Yu, Songqing Tang, Lei Wang, Xuetao Cao, Taoyong Chen
Various pattern recognition receptors (PRRs) are activated in response to viral infection to stimulate the production of type I interferons (IFNs). However, central to the responses of all of these receptors is their activation of the kinase TBK1, which stimulates transcription by IFN regulatory factor 3 (IRF3). We investigated the mechanism by which the kinase activity of TBK1 is stimulated in response to viral infection. We found that the tyrosine kinase Src promoted the phosphorylation of TBK1 on Tyr(179) upon viral infection of RAW264...
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28049150/fosl1-inhibits-type-i-interferon-responses-to-malaria-and-viral-infections-by-blocking-tbk1-and-traf3-trif-interactions
#4
Baowei Cai, Jian Wu, Xiao Yu, Xin-Zhuan Su, Rong-Fu Wang
: Innate immune response plays a critical role in controlling invading pathogens, but such an immune response must be tightly regulated. Insufficient or overactivated immune responses may lead to harmful or even fatal consequences. To dissect the complex host-parasite interactions and the molecular mechanisms underlying innate immune responses to infections, here we investigate the role of FOS-like antigen 1 (FOSL1) in regulating the host type I interferon (IFN-I) response to malaria parasite and viral infections...
January 3, 2017: MBio
https://www.readbyqxmd.com/read/28011393/astragaloside-iv-attenuates-cognitive-impairments-induced-by-transient-cerebral-ischemia-and-reperfusion-in-mice-via-anti-inflammatory-mechanisms
#5
Min Li, Hongyan Li, Fang Fang, Xueyang Deng, Shiping Ma
Astragaloside IV (AS-IV) is the main active component isolated from the traditional Chinese medicinal herb Astragalus membranaceus. Studies have demonstrated that AS-IV has neuroprotective effects in cerebral ischemic models. In this study, we aimed to investigate the effects of AS-IV on memory impairment induced by transient cerebral ischemia and reperfusion in mice, as well as the associated signaling mechanisms. Severe memory deficits were induced by bilateral common carotid artery occlusion (BCCAO) in mice as indicated in the Morris water maze test in this study...
December 21, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/28010888/dose-dependent-effects-of-morphine-on-lipopolysaccharide-lps-induced-inflammation-and-involvement-of-multixenobiotic-resistance-mxr-transporters-in-lps-efflux-in-teleost-fish
#6
Hélène Mottaz, Rene Schönenberger, Stephan Fischer, Rik I L Eggen, Kristin Schirmer, Ksenia J Groh
Opioid drugs, such as morphine (MO), detected in aquatic environments worldwide, may harm fish due to their semi-persistence and ability to potently interact with molecular targets conserved across vertebrates. Here, we established a waterborne bacterial lipopolysaccharide (LPS) challenge assay with zebrafish embryos as a model to investigate chemically-induced disruption of the innate immune system, and used it to study the effects of MO exposure. Exposure to 1 mg/L MO resulted in pronounced immunosuppression, reflected in downregulation of several inflammation-related genes, including myd88, trif, traf6, p38, nfκb2, il-1β, il-8 and ccl34a...
February 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28007523/pinocembrin-protects-hemorrhagic-brain-primarily-by-inhibiting-toll-like-receptor-4-and-reducing-m1-phenotype-microglia
#7
Xi Lan, Xiaoning Han, Qian Li, Qiang Li, Yufeng Gao, Tian Cheng, Jieru Wan, Wei Zhu, Jian Wang
Neuroinflammation is a major contributor to intracerebral hemorrhage (ICH) progression, but no drug is currently available to reduce this response and protect against ICH-induced injury. Recently, the natural product pinocembrin has been shown to ameliorate neuroinflammation and is undergoing a phase II clinical trial for ischemic stroke treatment. In this study, we examined the efficacy of pinocembrin in an ICH model, and further examined its effect on microglial activation and polarization. In vivo, pinocembrin dose-dependently reduced lesion volume by ∼47...
December 20, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27997892/the-role-of-tlr4-in-m1-macrophage-induced-epithelial-mesenchymal-transition-of-peritoneal-mesothelial-cells
#8
Jun Shi, Qing Li, Meixiao Sheng, Min Zheng, Manshu Yu, Lu Zhang
BACKGROUND/AIMS: Peritoneal fibrosis is a frequent complication of peritoneal dialysis that follows inflammation. It is recognized that epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs), plays a key role in fibrogenesis. However, the relationship between inflammatory macrophages and PMCs remains elusive. In this study, we investigated the effects of different polarized macrophages on EMT of HMrSV5 PMCs. METHODS: Monocytes were polarized to M1/M2 macrophages before being added to HMrSV5 in direct or indirect contact...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27912060/the-hippo-pathway-kinases-lats1-2-suppress-cancer-immunity
#9
Toshiro Moroishi, Tomoko Hayashi, Wei-Wei Pan, Yu Fujita, Matthew V Holt, Jun Qin, Dennis A Carson, Kun-Liang Guan
Poorly immunogenic tumor cells evade host immunity and grow even in the presence of an intact immune system, but the complex mechanisms regulating tumor immunogenicity have not been elucidated. Here, we discovered an unexpected role of the Hippo pathway in suppressing anti-tumor immunity. We demonstrate that, in three different murine syngeneic tumor models (B16, SCC7, and 4T1), loss of the Hippo pathway kinases LATS1/2 (large tumor suppressor 1 and 2) in tumor cells inhibits tumor growth. Tumor regression by LATS1/2 deletion requires adaptive immune responses, and LATS1/2 deficiency enhances tumor vaccine efficacy...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27908440/lipid-raft-dependent-endocytosis-negatively-regulates-responsiveness-of-j774-macrophage-like-cells-to-lps-by-down-regulating-the-cell-surface-expression-of-lps-receptors
#10
Szczepan Józefowski, Małgorzata Śróttek
Acting through CD14 and TLR4/MD-2, lipopolysaccharide (LPS) triggers strong pro-inflammatory activation of macrophages, which, if not appropriately controlled, may lead to lethal septic shock. Therefore, numerous mechanisms of negative regulation of responses to LPS exist, but whether they include down-regulation of LPS receptors is not clear. We have found that in J774 cells, the clathrin-dependent endocytic pathway enables activation of TRIF-dependent TLR4 signaling within endosomes, but is not associated with the down-regulation of TLR4 or CD14 surface expression...
November 23, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/27891130/molecular-mechanisms-that-underlie-the-dynamic-adaptation-of-innate-monocyte-memory-to-varying-stimulant-strength-of-tlr-ligands
#11
Ruoxi Yuan, Shuo Geng, Liwu Li
In adaptation to rising stimulant strength, innate monocytes can be dynamically programed to preferentially express either pro- or anti-inflammatory mediators. Such dynamic innate adaptation or programing may bear profound relevance in host health and disease. However, molecular mechanisms that govern innate adaptation to varying strength of stimulants are not well understood. Using lipopolysaccharide (LPS), the model stimulant of toll-like-receptor 4 (TLR4), we reported that the expressions of pro-inflammatory mediators are preferentially sustained in monocytes adapted by lower doses of LPS, and suppressed/tolerized in monocytes adapted by higher doses of LPS...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27881733/lysosomal-trafficking-regulator-lyst-links-membrane-trafficking-to-toll-like-receptor-mediated-inflammatory-responses
#12
Andreas Westphal, Weijia Cheng, Jinbo Yu, Guntram Grassl, Martina Krautkrämer, Otto Holst, Niko Föger, Kyeong-Hee Lee
Subcellular compartmentalization of receptor signaling is an emerging principle in innate immunity. However, the functional integration of receptor signaling pathways into membrane trafficking routes and its physiological relevance for immune responses is still largely unclear. In this study, using Lyst-mutant beige mice, we show that lysosomal trafficking regulator Lyst links endolysosomal organization to the selective control of toll-like receptor 3 (TLR3)- and TLR4-mediated proinflammatory responses. Consequently, Lyst-mutant mice showed increased susceptibility to bacterial infection and were largely resistant to endotoxin-induced septic shock...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27872207/myeloid-specific-gene-deletion-of-protein-phosphatase-2a-magnifies-myd88-and-trif-dependent-inflammation-following-endotoxin-challenge
#13
Lei Sun, Tiffany T Pham, Timothy T Cornell, Kelli L McDonough, Walker M McHugh, Neal B Blatt, Mary K Dahmer, Thomas P Shanley
Protein phosphatase 2A (PP2A) is a member of the intracellular serine/threonine phosphatases. Innate immune cell activation triggered by pathogen-associated molecular patterns is mediated by various protein kinases, and PP2A plays a counter-regulatory role by deactivating these kinases. In this study, we generated a conditional knockout of the α isoform of the catalytic subunit of PP2A (PP2ACα). After crossing with myeloid-specific cre-expressing mice, effective gene knockout was achieved in various myeloid cells...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27862204/a-comparison-of-the-immunological-potency-of-burkholderia-lipopolysaccharides-in-endotoxemic-balb-c-mice
#14
Pei-Tan Hsueh, Chiu-Lin Liu, Hsuan-Han Wang, Wei-Fen Ni, Ya-Lei Chen, Jong-Kang Liu
Lipopolysaccharide is one of the virulence factors of the soil-borne pathogens Burkholderia pseudomallei, B. thailandensis, B. cenocepacia and B. multivorans, which cause septic melioidosis (often in B. pseudomallei infections but rarely in B. thailandensis infections) or cepacia syndromes (commonly in B. cenocepacia infections but rarely in B. multivorans infections). The inflammatory responses in Burkholderia LPS-induced endotoxemia were evaluated in this study. Prior to induction, the conserved structures and functions of each purified LPS were determined using electrophoretic phenotypes, the ratios of 3-hydroxytetradecanoic to 3-hydroxyhexadecanoic acid and endotoxin units...
November 2016: Microbiology and Immunology
https://www.readbyqxmd.com/read/27853628/tir-domain-containing-adapter-inducing-interferon-%C3%AE-trif-regulates-cxcr5-t-helper-cells-in-the-intestine
#15
Saravana Kanagavelu, Claudia Flores, Shinichiro Hagiwara, Jose Ruiz, Jinhee Hyun, Ei E Cho, Frank Sun, Laura Romero, David Q Shih, Masayuki Fukata
OBJECTIVE: Establishing an effective humoral immunity is an important host defense mechanism in intestinal mucosa. T follicular helper (Tfh) cells are a spectrum of CXCR5 expressing T helper cells that induce antigen-specific B cell differentiation. Because the differentiation of T helper cells is largely regulated by innate immunity, we addressed whether TRIF signaling regulates Tfh cell differentiation and its ability to trigger humoral immune responses in the intestine. METHOD: CD4(+)CXCR5(+) T cells, B cells, and plasma cells in the Peyer's patches (PPs) of WT and TRIF-deficient (Trif(LPS2)) mice were analyzed by flow cytometry at the baseline, 9 days post primary infection, and 7 days post-secondary infection with Y...
October 2016: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/27847343/fish-trim32-functions-as-a-critical-antiviral-molecule-against-iridovirus-and-nodavirus
#16
Yepin Yu, Xiaohong Huang, Jiaxin Liu, Jingcheng Zhang, Yin Hu, Ying Yang, Youhua Huang, Qiwei Qin
Tripartite motif-containing 32 (TRIM32) has been demonstrated to pay vital roles in cancer, genetic disorders and antiviral immunity. However, the molecular functions of fish TRIM32 still remained largely unknown. Here, a novel TRIM32 gene from orange spotted grouper (EcTRIM32) was cloned and characterized. EcTRIM32 encoded a 685-aa protein which showed 93%, and 60% identity to large yellow croaker (Larimichthys crocea) and human (Homo sapiens), respectively. Amino acid alignment showed that EcTRIM32 contained a conserved RING-finger domain, a BBOX domain and NHL domain...
November 12, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27830882/histological-changes-in-the-vulva-and-vagina-from-ovariectomised-rats-undergoing-oestrogen-treatment
#17
R F Mocan-Hognogi, N Costin, A Malutan, R Ciortea, I A Trif, A L Nagy, M L Bogdan, D Mihu
BACKGROUND: The purpose of this study was to assess the histological changes occurring in the vagina and vulva in ovariectomised female rats, as well as the response to the administration of injectable oestrogens. MATERIAL AND METHODS: We used 30 female Wistar white rats, distributed as follows: group 1 - the control group, group 2 - the operated but untreated rats, and groups 3, 4 and 5 - operated rats, to which oestrogenic treatment was administered (Estradiol, Estradurin, Sintofolin) at a dosage of 0...
2016: Folia Morphologica (Warsz)
https://www.readbyqxmd.com/read/27810900/endoplasmic-reticulum-stress-induced-hepatocellular-death-pathways-mediate-liver-injury-and-fibrosis-via-stimulator-of-interferon-genes
#18
Arvin Iracheta-Vellve, Jan Petrasek, Benedek Gyongyosi, Abhishek Satishchandran, Patrick Lowe, Karen Kodys, Donna Catalano, Charles D Calenda, Evelyn A Kurt-Jones, Katherine A Fitzgerald, Gyongyi Szabo
Fibrosis, driven by inflammation, marks the transition from benign to progressive stages of chronic liver diseases. Although inflammation promotes fibrogenesis, it is not known whether other events, such as hepatocyte death, are required for the development of fibrosis. Interferon regulatory factor 3 (IRF3) regulates hepatocyte apoptosis and production of type I IFNs. In the liver, IRF3 is activated via Toll-like receptor 4 (TLR4) signaling or the endoplasmic reticulum (ER) adapter, stimulator of interferon genes (STING)...
December 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27755506/sting-and-trif-contribute-to-mouse-sepsis-depending-on-severity-of-the-disease-model
#19
Erica L Heipertz, Jourdan Harper, Wendy E Walker
IFN regulatory factor (IRF)3 plays a detrimental role in the cecal ligation and puncture (CLP) mouse model of sepsis. However, it is unclear which pathway activates IRF3 in this context. In this report we investigate two pathways that activate IRF3: the Stimulator of Interferon Genes (STING) pathway (which senses cytosolic DNA) and the TIR-domain-containing adapter-inducing interferon-β (TRIF) pathway (which sense dsRNA and LPS via Toll-like receptor (TLR) 3 and 4). Initially, we examine the impact of these pathways using a severe CLP model (∼90% mortality)...
October 17, 2016: Shock
https://www.readbyqxmd.com/read/27748405/disabled-2-is-a-negative-immune-regulator-of-lipopolysaccharide-stimulated-toll-like-receptor-4-internalization-and-signaling
#20
Wei-Shan Hung, Pin Ling, Ju-Chien Cheng, Shy-Shin Chang, Ching-Ping Tseng
Toll-like receptor 4 (TLR4) plays a pivotal role in the host response to lipopolysaccharide (LPS), a major cell wall component of Gram-negative bacteria. Here, we elucidated whether the endocytic adaptor protein Disabled-2 (Dab2), which is abundantly expressed in macrophages, plays a role in LPS-stimulated TLR4 signaling and trafficking. Molecular analysis and transcriptome profiling of RAW264.7 macrophage-like cells expressing short-hairpin RNA of Dab2 revealed that Dab2 regulated the TLR4/TRIF pathway upon LPS stimulation...
October 17, 2016: Scientific Reports
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