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https://www.readbyqxmd.com/read/27903427/anti-inflammatory-effect-of-miltirone-on-inflammatory-bowel-disease-via-tlr4-nf-%C3%AE%C2%BAb-iqgap2-signaling-pathway
#1
Hongjian Wang, Junfei Gu, Xuefeng Hou, Juan Chen, Nan Yang, Ying Liu, Gang Wang, Mei Du, Huihui Qiu, Yi Luo, Ziyu Jiang, Liang Feng
Inflammatory bowel disease (IBD) is characterized by a radical imbalance in the activation of proinflammatory and anti-inflammatory signaling pathways in the gut. This study was conducted to evaluate the anti-inflammation effect of miltirone against IBD in vitro and in vivo, and try to explore the underlying mechanisms. Miltirone could extenuate the loss of colon length and weight caused by TNBS. Additionally, macroscopic scores and DAI were reduced significantly compared with the TNBS group. The levels of TNF-α, IL-1β, IL-6 and IL-8 were increased significantly with the induction by TNBS (100mg/kg) or LPS (0...
November 27, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27898007/limb-remote-ischemic-postconditioning-reduces-ischemia-reperfusion-injury-by-inhibiting-nadph-oxidase-activation-and-myd88-traf6-p38map-kinase-pathway-of-neutrophils
#2
Gangling Chen, Xinyi Ye, Jiangwei Zhang, Tingli Tang, Lin Li, Peirong Lu, Qi Wu, Boyang Yu, Junping Kou
Limb remote ischemic postconditioning (LRIP) has been confirmed to reduce the ischemia-reperfusion injury but its mechanisms are still not clear. This study clarified the mechanism of LRIP based on the nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase and Myeloid differentiation factor 88 (MyD88)-Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6)-P38 pathway of neutrophils. Rat middle cerebral artery occlusion (MCAO) model was used in this study. Ischemia-reperfusion injury was carried out by MCAO 1...
November 25, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27891130/molecular-mechanisms-that-underlie-the-dynamic-adaptation-of-innate-monocyte-memory-to-varying-stimulant-strength-of-tlr-ligands
#3
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/27890916/polydatin-ameliorates-staphylococcus-aureus-induced-mastitis-in-mice-via-inhibiting-tlr2-mediated-activation-of-the-p38-mapk-nf-%C3%AE%C2%BAb-pathway
#4
Kang-Feng Jiang, Gan Zhao, Gan-Zhen Deng, Hai-Chong Wu, Nan-Nan Yin, Xiu-Ying Chen, Chang-Wei Qiu, Xiu-Li Peng
Recent studies show that Polydatin (PD) extracted from the roots of Polygonum cuspidatum Sieb, a widely used traditional Chinese remedies, possesses anti-inflammatory activity in several experimental models. In this study, we investigated the anti-inflammatory effects of PD on Staphylococcus aureus-induced mastitis in mice and elucidated the potential mechanisms. In mice with S aureus-induced mastitis, administration of PD (15, 30, 45 mg/kg, ip) or dexamethasone (Dex, 5 mg/kg, ip) significantly suppressed the infiltration of inflammatory cells, ameliorated the mammary structural damage, and inhibited the activity of myeloperoxidase, a biomarker of neutrophils accumulation...
November 28, 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27890776/epigallocatechin-3-gallate-alleviates-paraquat-induced-acute-lung-injury-and-inhibits-upregulation-of-toll-like-receptors
#5
Haitao Shen, Na Wu, Zhenning Liu, Hongyu Zhao, Min Zhao
AIMS: To evaluate the detoxifying effect of epigallocatechin-3-gallate (EGCG) on paraquat (PQ)-induced acute lung injury in mice, and to explore the action mechanisms. MAIN METHODS: Following administration of PQ, the mice received a low, a medium or a high dose of EGCG daily for three days. Histopathology of the lungs were examined by H&E staining. The levels of inflammatory cytokines, such as TNF-α, IL-1β and IL-6, in the bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay...
November 24, 2016: Life Sciences
https://www.readbyqxmd.com/read/27890075/clone-specific-myd88-l265p-and-cxcr4-mutation-status-can-provide-clinical-utility-in-suspected-waldenstr%C3%A3-m-macroglobulinemia-lymphoplasmacytic-lymphoma
#6
Bettina Burnworth, Zhixing Wang, Timothy P Singleton, Angela Bennington, Wayne Fritschle, Richard Bennington, Lisa Eidenschink Brodersen, Denise A Wells, Michael R Loken, Barbara K Zehentner
MYD88 L265P, a diagnostic marker for lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM) can also be detected in other hematopoietic malignancies. We demonstrate a novel approach to increase the specificity of this marker for WM/LPL diagnosis by combining flow cytometric cell sorting with molecular analysis. Clonal B-lymphocyte and co-occurring clonal plasma cell populations of low-grade B-cell lymphomas were sorted by flow cytometry and analyzed for immunoglobulin gene rearrangements (PCR), and for MYD88 and CXCR4 mutations...
December 2016: Leukemia Research
https://www.readbyqxmd.com/read/27888719/treponema-pallidum-flagellin-flaa2-induces-il-6-secretion-in-thp-1-cells-via-the-toll-like-receptor-2-signaling-pathway
#7
Yafeng Xie, Man Xu, Yongjian Xiao, Zhuoran Liu, Chuanhao Jiang, Xingxing Kuang, Chuan Wang, Haiying Wu, Jing Peng, Chun Li, Yu Wang, Huaming Liu, Bin Liu, Xiaotuan Zhang, Feijun Zhao, Tiebing Zeng, Shuangquan Liu, Yimou Wu
Treponema pallidum subsp. pallidum membrane proteins are considered as potent inducers in the initiation and development of inflammation. In the present study, the mechanism that leads to the production of interleukin 6 (IL-6), one of the key proinflammatory cytokines, by human monocytic THP-1 cells when these cells are treated with T. pallidum flagellin FlaA2 was investigated. Stimulation with flagellin FlaA2 can induce IL-6 expression in human monocytes and augment the phosphorylation of ERK, p38, and NF-κB, but has no effect on the phosphorylation of JNK...
November 23, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27884809/construction-of-a-streptococcus-agalactiae-phob-mutant-and-evaluation-of-its-potential-as-an-attenuated-modified-live-vaccine-in-golden-pompano-trachinotus-ovatus
#8
Xiaohui Cai, Bei Wang, Yinhui Peng, Yuan Li, Yishan Lu, Yucong Huang, Jichang Jian, Zaohe Wu
Streptococcus agalactiae is a Gram-positive pathogen that can survive inside professional phagocytes and nonphagocytic cells to cause septicemia and meningoencephalitis in freshwater and marine fish. However, vaccines based on extracellular products (ECP) and formalin-killed whole S. agalactiae cells, as well as subunit vaccine are unable to protect fish from infection by variant serotypes S. agalactiae. The search for live attenuated vaccine with highly conserved and virulent-related genes is essential for producing a vaccine to help understand and control streptococcosis In this study, the phoB gene was cloned from pathogenic S...
November 21, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27882228/oxymatrine-inhibits-microglia-activation-via-hsp60-tlr4-signaling
#9
Feijia Ding, Yunhong Li, Xiaolin Hou, Rui Zhang, Shuting Hu, Yin Wang
Oxymatrine (OMT) is an alkaloid extracted from Sophora flavescens, which has broad anti-inflammatory, antitumor and immunosuppressant actions. However, the underlying molecular mechanisms have remained elusive. Heat shock protein 60 (HSP60) has recently been shown to have an important role in autoimmune reactions. The present study aimed to investigate whether OMT exerts its anti-inflammatory effects by inhibiting microglial activation and examined the role of HSP60 in this process. Western blot analysis and ELISA showed that OMT decreased the expression and release of HSP60 by LPS-activated BV2 cells...
November 2016: Biomedical Reports
https://www.readbyqxmd.com/read/27878326/a-novel-72-kda-leukocyte-derived-osteoglycin-enhances-the-activation-of-toll-like-receptor-4-and-exacerbates-cardiac-inflammation-during-viral-myocarditis
#10
Marieke Rienks, Anna Papageorgiou, Kristiaan Wouters, Wouter Verhesen, Rick van Leeuwen, Paolo Carai, Georg Summer, Dirk Westermann, Stephane Heymans
BACKGROUND: Viral myocarditis can severely damage the myocardium through excessive infiltration of immune cells. Osteoglycin (OGN) is part of the small leucine-rich repeat proteoglycan (SLRP) family. SLRP's may affect inflammatory and fibrotic processes, but the implication of OGN in cardiac inflammation and the resulting injury upon viral myocarditis is unknown. METHODS AND RESULTS: This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis...
November 23, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27876844/the-n-terminal-loop-of-irak-4-death-domain-regulates-ordered-assembly-of-the-myddosome-signalling-scaffold
#11
Anthony C G Dossang, Precious G Motshwene, Yang Yang, Martyn F Symmons, Clare E Bryant, Satty Borman, Julie George, Alexander N R Weber, Nicholas J Gay
Activation of Toll-like receptors induces dimerization and the recruitment of the death domain (DD) adaptor protein MyD88 into an oligomeric post receptor complex termed the Myddosome. The Myddosome is a hub for inflammatory and oncogenic signaling and has a hierarchical arrangement with 6-8 MyD88 molecules assembling with exactly 4 of IRAK-4 and 4 of IRAK-2. Here we show that a conserved motif in IRAK-4 (Ser8-X-X-X-Arg12) is autophosphorylated and that the phosphorylated DD is unable to form Myddosomes. Furthermore a mutant DD with the phospho-mimetic residue Asp at this position is impaired in both signalling and Myddosome assembly...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27876571/fusobacterium-nucleatum-increases-proliferation-of-colorectal-cancer-cells-and-tumor-development-in-mice-by-activating-tlr4-signaling-to-nf%C3%AE%C2%BAb-upregulating-expression-of-microrna-21
#12
Yongzhi Yang, Wenhao Weng, Junjie Peng, Leiming Hong, Lei Yang, Yuji Toiyama, Renyuan Gao, Minfeng Liu, Mingming Yin, Cheng Pan, Hao Li, Bomin Guo, Qingchao Zhu, Qing Wei, Mary-Pat Moyer, Ping Wang, Sanjun Cai, Ajay Goel, Huanlong Qin, Yanlei Ma
BACKGROUND & AIMS: Nearly 20% of the global cancer burden can be linked to infectious agents. Fusobacterium nucleatum promotes tumor formation by epithelial cells via unclear mechanisms. We aimed to identify microRNAs (miRNAs) induced by F nucleatum and evaluate their ability to promote colorectal carcinogenesis in mice. METHODS: Colorectal cancer (CRC) cell lines were incubated with F nucleatum or control reagents and analyzed in proliferation and would healing assays...
November 19, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27875107/the-effect-of-elevated-intra-abdominal-pressure-on-tlr4-signaling-in-intestinal-mucosa-and-on-intestinal-bacterial-translocation-in-a-rat
#13
Adam Strier, Dragan Kravarusic, Arnold G Coran, Isaac Srugo, Nir Bitterman, Tatiana Dorfman, Yulia Pollak, Ibrahim Matter, Igor Sukhotnik
BACKGROUND: Recent evidence suggests that elevated intra-abdominal pressure (IAP) may adversely affect the intestinal barrier function. Toll-like receptor 4 (TLR-4) is responsible for the recognition of bacterial endotoxin or lipopolysaccharide and for initiation of the Gram-negative septic shock syndrome. The objective of the current study was to determine the effects of elevated IAP on intestinal bacterial translocation (BT) and TLR-4 signaling in intestinal mucosa in a rat model. METHODS: Male Sprague-Dawley rats were randomly assigned to one of two experimental groups: sham animals (Sham) and IAP animals who were subjected to a 15 mmHg pressure pneumoperitoneum for 30 minutes...
November 22, 2016: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A
https://www.readbyqxmd.com/read/27872237/flagellin-mediated-protection-against-intestinal-yersinia-pseudotuberculosis-infection-does-not-require-interleukin-22
#14
Rémi Porte, Laurye Van Maele, Natalia Muñoz-Wolf, Benoit Foligné, Laure Dumoutier, Julien Tabareau, Delphine Cayet, Pierre Gosset, Nicolas Jonckheere, Isabelle Van Seuningen, A José Chabalgoity, Michel Simonet, Mohamed Lamkanfi, Jean-Christophe Renauld, Jean-Claude Sirard, Christophe Carnoy
Signaling through toll-like receptors (TLRs), the main receptors in innate immunity, is essential for the defense of mucosal surfaces. It was previously shown that systemic TLR5 stimulation by bacterial flagellin induces an immediate, transient interleukin-22 (IL-22)-dependent antimicrobial response to bacterial or viral infections of the mucosa. This process was dependent on the activation of type 3 innate lymphoid cells (ILCs). The objective of the present study was to analyze the effects of flagellin treatment in a murine model of oral infection with Yersinia pseudotuberculosis (an invasive, Gram-negative, enteropathogenic bacterium that targets the small intestine)...
November 21, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27872207/myeloid-specific-gene-deletion-of-protein-phosphatase-2a-magnifies-myd88-and-trif-dependent-inflammation-following-endotoxin-challenge
#15
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...
November 21, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27870876/reduced-picd-in-monocytes-mounts-altered-neonate-immune-response-to-candida-albicans
#16
Stephan Dreschers, Peter Saupp, Mathias Hornef, Andrea Prehn, Christopher Platen, Joachim Morschhäuser, Thorsten W Orlikowsky
BACKGROUND: Invasive fungal infections with Candida albicans (C. albicans) occur frequently in extremely low birthweight (ELBW) infants and are associated with poor outcome. Phagocytosis of C.albicans initializes apoptosis in monocytes (phagocytosis induced cell death, PICD). PICD is reduced in neonatal cord blood monocytes (CBMO). HYPOTHESIS: Phagocytosis of C. albicans causes PICD which differs between neonatal monocytes (CBMO) and adult peripheral blood monocytes (PBMO) due to lower stimulation of TLR-mediated immune responses...
2016: PloS One
https://www.readbyqxmd.com/read/27869651/pericyte-myd88-and-irak4-control-inflammatory-and-fibrotic-responses-to-tissue-injury
#17
Irina A Leaf, Shunsaku Nakagawa, Bryce G Johnson, Jin Joo Cha, Kristen Mittelsteadt, Kevin M Guckian, Ivan G Gomez, William A Altemeier, Jeremy S Duffield
Fibrotic disease is associated with matrix deposition that results in the loss of organ function. Pericytes, the precursors of myofibroblasts, are a source of pathological matrix collagens and may be promising targets for treating fibrogenesis. Here, we have shown that pericytes activate a TLR2/4- and MyD88-dependent proinflammatory program in response to tissue injury. Similarly to classic immune cells, pericytes activate the NLRP3 inflammasome, leading to IL-1β and IL-18 secretion. Released IL-1β signals through pericyte MyD88 to amplify this response...
November 21, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27866535/-regulatory-analysis-of-hypoxia-on-innate-immunity-of-human-corneal-epithelium
#18
K P Pang, H Pan, X Y Wu
Objective: To investigate the role of hypoxia on the regulation of innate immunity of human corneal epithelium. Methods: Telomerase-immortalized human epithelial cells (THCEs) were incubated under normoxia (21% O2) or hypoxic (1% O2) conditions respectively. After 6, 12, 24, 48 h culture, the mRNA and protein levels of toll like receptor 4 (TLR4) were measured by real-time polymerase chain reaction (RT-PCR) and Western blot analysis. After 24 h culture, THCEs of each group were challenged respectively with TLR4 ligand lipopolysaccharide (LPS) (1 μg/ml) for 6 h...
November 15, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27864528/irak1-and-irak4-promote-phosphorylation-ubiquitination-and-degradation-of-myd88-adaptor-like-mal
#19
Aisling Dunne, Susan Carpenter, Constantinos Brikos, Pearl Gray, Astrid Strelow, Holger Wesche, Nick Morrice, Luke A J O'Neill
No abstract text is available yet for this article.
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27864347/human-pancreatic-cancer-cells-induce-a-myd88-dependent-stromal-response-to-promote-a-tumor-tolerant-immune-microenvironment
#20
Daniel Delitto, Andrea E Delitto, Bayli B DiVita, Kien Pham, Song Han, Emily R Hartlage, Brittney N Newby, Michael H Gerber, Kevin E Behrns, Lyle L Moldawer, Ryan M Thomas, Thomas George, Todd Brusko, Clayton E Mathews, Chen Liu, Jose G Trevino, Steven J Hughes, Shannon Wallet
Cancer cells exert mastery over the local tumor-associated stroma (TAS) to configure protective immunity within the tumor microenvironment. The immunomodulatory character of pancreatic lysates of patients with cancer differs from those with pancreatitis. In this study, we evaluated the crosstalk between pancreatic cancer (PC) and its TAS in primary human cell culture models. Upon exposure of TAS to PC cell-conditioned media, we documented robust secretion of IL-6 and IL-8. This TAS response was MyD88-dependent and sufficient to directly suppress both CD4+ and CD8+ T cell proliferation, inducing Th17 polarization at the expense of Th1...
November 18, 2016: Cancer Research
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