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https://www.readbyqxmd.com/read/28647362/farnesoid-x-receptor-agonist-gw4064-ameliorates-lipopolysaccharide-induced-ileocolitis-through-tlr4-myd88-pathway-related-mitochondrial-dysfunction-in-mice
#1
Hsuan-Miao Liu, Jyh-Fe Liao, Tzung-Yan Lee
Inflammatory bowel disease (IBD) is a complex and relapsing inflammatory condition of the gastro intestinal tract characterized by diarrhea and abdominal pain. Farnesoid X receptor (FXR) plays an important role in enteroprotection and mucosal injury by regulating inflammatory responses and barrier function in the intestinal tract. Here we show the mechanisms of FXR agonist, GW4064, inhibits mucosal injury in ileum caused by lipopolysaccharides (LPS). Ileum injury was induced by intraperitoneal injection of LPS in Wild-type (WT) and FXR knockout (KO) mice...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28646802/dampness-can-promote-the-influenza-a-virus-and-worsen-its-prognosis-by-upregulating-the-tlr7-signaling-pathway
#2
Deng Li, Xu Huachong, Pang Peng, Zheng Ke, Nie Jiao, Wu Xianlin, Yu Bin, Chen Jia, Chen Xiaoyin
Context • Outbreaks of the influenza A virus (IAV) are increasingly recognized as a global public health issue, affecting a large proportion of the world's population. A number of studies have provided epidemiologic evidence that dampness and mold are consistently associated with multiple allergic and respiratory effects, but they focused on dampness-related pathogenic microorganisms leading to allergy rather than the dampness itself. Objective • The current study intended to examine the effects of a damp environment on the promotion of the IAV and determine the adverse effects on its prognosis through upregulation of the toll-like receptor 7 (TLR7)-signaling pathway in the lung...
June 23, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28646187/microrna-148-as-a-negative-regulator-of-the-common-tlr-adaptor-mediates-inflammatory-response-in-teleost-fish
#3
Qing Chu, Yunhang Gao, Dekun Bi, Tianjun Xu
MicroRNAs are small endogenous noncoding RNAs implicating in the regulation of diverse biological processes, including proliferation, differentiation, cancer, apoptosis, and viral infections. MicroRNAs regulate gene expression by either mRNA degradation or inhibition of protein translation. Although microRNAs have emerged as important controller involved in regulation of inflammatory response, the microRNA-mediated regulatory mechanism remains less clear in teleost. Here, we report that miR-148 targets MyD88 and down-regulates its expression by inhibition protein translation rather than degradation mRNA in miiuy croaker...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645296/myd88-dependent-pro-interleukin-1%C3%AE-induction-in-dendritic-cells-exposed-to-food-grade-synthetic-amorphous-silica
#4
Hans Christian Winkler, Julian Kornprobst, Peter Wick, Lea Maria von Moos, Ioannis Trantakis, Elisabeth Maria Schraner, Barbara Bathke, Hubertus Hochrein, Mark Suter, Hanspeter Naegeli
BACKGROUND: Dendritic cells (DCs) are specialized first-line sensors of foreign materials invading the organism. These sentinel cells rely on pattern recognition receptors such as Nod-like or Toll-like receptors (TLRs) to launch immune reactions against pathogens, but also to mediate tolerance to self-antigens and, in the intestinal milieu, to nutrients and commensals. Since inappropriate DC activation contributes to inflammatory diseases and immunopathologies, a key question in the evaluation of orally ingested nanomaterials is whether their contact with DCs in the intestinal mucosa disrupts this delicate homeostatic balance between pathogen defense and tolerance...
June 23, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28644138/comparative-analysis-of-primary-versus-relapse-refractory-dlbcl-identifies-shifts-in-mutation-spectrum
#5
Danielle M Greenawalt, Winnie S Liang, Sakina Saif, Justin Johnson, Petar Todorov, Austin Dulak, Daniel Enriquez, Rebecca Halperin, Ambar Ahmed, Vladislav Saveliev, John Carpten, David Craig, J Carl Barrett, Brian Dougherty, Michael Zinda, Stephen Fawell, Jonathan R Dry, Kate Byth
Current understanding of the mutation spectrum of relapsed/refractory (RR) tumors is limited. We performed whole exome sequencing (WES) on 47 diffuse large B cell lymphoma (DLBCL) tumors that persisted after R-CHOP treatment, 8 matched to primary biopsies. We compared genomic alterations from the RR cohort against two treatment-naïve DLBCL cohorts (n=112). While the overall number and types of mutations did not differ significantly, we identified frequency changes in DLBCL driver genes. The overall frequency of MYD88 mutant samples increased (12% to 19%), but we noted a decrease in p...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28642279/role-of-myd88-signaling-in-the-imiquimod-induced-mouse-model-of-psoriasis-focus-on-innate-myeloid-cells
#6
Sara Costa, Olivia Marini, Dalila Bevilacqua, Anthony L DeFranco, Baidong Hou, Silvia Lonardi, William Vermi, Pamela Rodegher, Anna Panato, Franco Tagliaro, Clifford A Lowell, Marco A Cassatella, Giampiero Girolomoni, Patrizia Scapini
Psoriasis is a chronic skin disease associated with deregulated activation of immune cells and keratinocytes. In this study, we used the imiquimod (IMQ)-induced mouse model of psoriasis to dissect better the contribution of hematopoietic and skin-resident stromal cells to psoriasis development. The comparison of disease development in mice carrying the hematopoietic cell-specific deletion of MyD88 (Myd88(fl/fl)Vav-cre(+) mice) with mice carrying the total MyD88 deficiency (Myd88(-/-) mice), we show that the progression of skin and systemic inflammation, as well as of epidermal thickening, was completely dependent on MyD88 expression in hematopoietic cells...
June 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28640392/calcineurin-inhibitors-exacerbate-coronary-arteritis-via-the-myd88-signaling-pathway-in-a-murine-model-of-kawasaki-disease
#7
Kenji Murata, Yoshitomo Motomura, Tamami Tanaka, Shunsuke Kanno, Takahisa Yano, Mitsuho Onimaru, Atsushi Shimoyama, Hisanori Nishio, Yasunari Sakai, Masatsugu Oh-Hora, Hiromitsu Hara, Koichi Fukase, Hidetoshi Takada, Satohiro Masuda, Shouichi Ohga, Sho Yamasaki, Toshiro Hara
Calcineurin inhibitors (CNIs) have been used off-label for the treatment of refractory Kawasaki disease (KD). However, it remains unknown whether CNIs show protective effects against the development of coronary artery lesions in KD patients. To investigate the effects of CNIs on coronary arteries and the mechanisms of their actions on coronary arteritis in a mouse model of KD, we performed experiments with FK565, a ligand of nucleotide-binding oligomerization domain-containing protein 1 (Nod1) in wild-type, SCID, CARD9(-/-) , and MyD88(-/-) mice...
June 22, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28636991/non-invasive-detection-of-somatic-mutations-using-next-generation-sequencing-in-primary-central-nervous-system-lymphoma
#8
Maxime Fontanilles, Florent Marguet, Élodie Bohers, Pierre-Julien Viailly, Sydney Dubois, Philippe Bertrand, Vincent Camus, Sylvain Mareschal, Philippe Ruminy, Catherine Maingonnat, Stéphane Lepretre, Elena-Liana Veresezan, Stéphane Derrey, Hervé Tilly, Jean-Michel Picquenot, Annie Laquerrière, Fabrice Jardin
PURPOSE: Primary central nervous system lymphomas (PCNSL) have recurrent genomic alterations. The main objective of our study was to demonstrate that targeted sequencing of circulating cell-free DNA (cfDNA) released by PCNSL at the time of diagnosis could identify somatic mutations by next-generation sequencing (NGS). PATIENTS AND METHODS: PlasmacfDNA and matched tumor DNA (tDNA) from 25 PCNSL patients were sequenced using an Ion Torrent Personal Genome Machine (Life Technologies®)...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28630328/toll-like-receptor-pathway-evolution-in-deuterostomes
#9
Michael G Tassia, Nathan V Whelan, Kenneth M Halanych
Animals have evolved an array of pattern-recognition receptor families essential for recognizing conserved molecular motifs characteristic of pathogenic microbes. One such family is the Toll-like receptors (TLRs). On pathogen binding, TLRs initiate specialized cytokine signaling catered to the class of invading pathogen. This signaling is pivotal for activating adaptive immunity in vertebrates, suggesting a close evolutionary relationship between innate and adaptive immune systems. Despite significant advances toward understanding TLR-facilitated immunity in vertebrates, knowledge of TLR pathway evolution in other deuterostomes is limited...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28628927/curcumin-promotes-apoptosis-of-activated-hepatic-stellate-cells-by-inhibiting-protein-expression-of-the-myd88-pathway
#10
Ya-Jun He, Kenny Kuchta, Yan-Mei Deng, Silke Cameron, Yu Lin, Xu-You Liu, Guo-Ron Ye, Xia Lv, Yuta Kobayashi, Jian-Chang Shu
Activation and proliferation of hepatic stellate cells (HSC) play an important role in the progress of liver fibrosis. HSC activation occurs in response to inflammatory cytokines, cellular interactions with immune cells, and morphogenetic signals. The literature hints to a role of the adaptor protein MyD88 in fibrosis. Although curcumin has been shown to exert inhibitory effects on the proliferation of HSC in vitro, its influence on the MyD88 pathway in HSC has remained unclear. Here, we investigated whether curcumin accelerates apoptosis of HSC through the MyD88 pathway...
June 19, 2017: Planta Medica
https://www.readbyqxmd.com/read/28626833/the-lung-is-a-host-defense-niche-for-immediate-neutrophil-mediated-vascular-protection
#11
Bryan G Yipp, Jung Hwan Kim, Ronald Lima, Lori D Zbytnuik, Björn Petri, Nick Swanlund, May Ho, Vivian G Szeto, Tamar Tak, Leo Koenderman, Peter Pickkers, Anton T J Tool, Taco W Kuijpers, Timo K van den Berg, Mark R Looney, Matthew F Krummel, Paul Kubes
Bloodstream infection is a hallmark of sepsis, a medically emergent condition requiring rapid treatment. However, upregulation of host defense proteins through toll-like receptors and NFκB requires hours after endotoxin detection. Using confocal pulmonary intravital microscopy, we identified that the lung provides a TLR4-Myd88-and abl tyrosine kinase-dependent niche for immediate CD11b-dependent neutrophil responses to endotoxin and Gram-negative bloodstream pathogens. In an in vivo model of bacteremia, neutrophils crawled to and rapidly phagocytosed Escherichia coli sequestered to the lung endothelium...
April 28, 2017: Science Immunology
https://www.readbyqxmd.com/read/28625885/dock8-deficiency-insights-into-pathophysiology-clinical-features-and-management
#12
REVIEW
Catherine M Biggs, Sevgi Keles, Talal A Chatila
Dedicator of Cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency that exemplifies the broad clinical features of primary immunodeficiencies (PIDs), extending beyond recurrent infections to include atopy, autoimmunity and cancer. It is caused by loss of function mutations in DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes that regulates the actin cytoskeleton. Additional roles of DOCK8 have also emerged, including regulating MyD88-dependent Toll-like receptor signaling and the activation of the transcription factor STAT3...
June 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28623125/chronic-intermittent-hypoxia-induces-liver-fibrosis-in-mice-with-diet-induced-obesity-via-tlr4-myd88-mapk-nf-kb-signaling-pathways
#13
Hyeon Hui Kang, In Kyoung Kim, Hye In Lee, Hyonsoo Joo, Jeong Uk Lim, Jongmin Lee, Sang Haak Lee, Hwa Sik Moon
Obstructive sleep apnea (OSA) is associated with nonalcoholic fatty liver disease (NAFLD), and causes chronic intermittent hypoxia (CIH) during sleep. Inflammation is associated with the development of metabolic complications induced by CIH. Research suggests that innate immune mechanisms are involved in the pro-inflammatory pathways of liver fibrosis. The purpose of this study was to investigate whether innate immune responses induce liver fibrosis, and to evaluate mechanisms underlying hepatic inflammation related to CIH in a murine diet-induced obesity (DIO) model...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28621230/lncrna-crnde-triggers-inflammation-through-the-tlr3-nf-%C3%AE%C2%BAb-cytokine-signaling-pathway
#14
Haowen Li, Qi Li, Tao Guo, Wenyan He, Chengya Dong, Yajie Wang
Colorectal neoplasia differentially expressed (CRNDE), an oncogene, is highly expressed in many tumor cells and affects cellular proliferation, migration, invasion, and apoptosis. Its function and mechanism of action is a research hotspot. In this study, microarray analysis was performed to discover the differentially expressed genes in CRNDE over-expression cells. RT² Profiler PCR Array was used to study the expression of genes related to the toll-like receptor (TLR) pathway. We found that over-expression of CRNDE in astrocytes increased the expression of key factors in the toll-like receptor signaling pathway, especially toll-like receptor-3-mediated MyD88-independent pathway...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28619997/cardiotonic-steroids-stimulate-macrophage-inflammatory-responses-through-a-pathway-involving-cd36-tlr4-and-na-k-atpase
#15
Yiliang Chen, Wenxin Huang, Moua Yang, Gang Xin, Weiguo Cui, Zijian Xie, Roy L Silverstein
OBJECTIVE: Circulating levels of cardiotonic steroids (CTS) are elevated in various chronic inflammatory conditions, but the role of CTS in inflammation remains largely unknown. We have previously shown that the CTS ouabain stimulates proinflammatory responses in murine macrophages. In this study, we aim to explore the mechanism how CTS induce proinflammatory responses in primary murine and human macrophages. APPROACH AND RESULTS: Using both murine peritoneal macrophages and human monocyte-derived macrophages, we demonstrated that ouabain activated NF-κB, leading to proinflammatory cytokine (eg, MCP-1, tumor necrosis factor-α, interleukin-1β, and interleukin-6) production...
June 15, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28617062/novel-approaches-to-targeting-myd88-in-waldenstr%C3%A3-m-macroglobulinemia
#16
Jorge J Castillo, Zachary R Hunter, Guang Yang, Steven P Treon
Waldenström macroglobulinemia (WM) is an incurable lymphoma characterized by the accumulation of IgM-producing lymphoplasmacytic cells in the bone marrow and other organs. Although WM patients can experience prolonged remissions, the disease invariably recurs advocating for the need of novel treatments in order to achieve higher response and survival rates. The discovery of a recurrent mutation in the MYD88 gene and an increased understanding behind the biology of MYD88 signaling have provided the opportunity to developing novel agents targeting the MYD88 pathway...
June 15, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28616865/isoacteoside-a-dihydroxyphenylethyl-glycoside-exhibits-anti-inflammatory-effects-through-blocking-tlr4-dimerization
#17
Hongwei Gao, Yankun Cui, Naixin Kang, Xin Liu, Yanli Liu, Yue Zou, Ziyu Zhang, Xiaoran Li, Shilin Yang, Ji Li, Chunming Wang, Qiong-Ming Xu, Xiuping Chen
BACKGROUND AND PURPOSE: Isoacteoside (ISO) is a phenylethanoid isolated from Monochasma savatieri Franch. ex Maxim., which is an anti-inflammatory herb widely used in traditional Chinese medicine. However, the exact mechanism of the anti-inflammatory activity of ISO is not completely understood. In this study, its anti-inflammatory mechanism in mouse macrophages was elucidated. EXPERIMENTAL APPROACH: The expression of the NF-κB pathway, MAPK pathway, iNOS, TNF-α, IL-6 and IL-1β was evaluated using western blotting, qRT-PCR or ELISA...
June 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28615695/brain-derived-neurotrophic-factor-is-regulated-via-myd88-nf-%C3%AE%C2%BAb-signaling-in-experimental-streptococcus-pneumoniae-meningitis
#18
Danfeng Xu, Di Lian, Zhijie Zhang, Ying Liu, Jiaming Sun, Ling Li
Streptococcus pneumoniae meningitis is an intractable disease of the central nervous system (CNS). Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic family and found to participate in the immune inflammatory response. In this study, we investigated if activation of the classical inflammatory signaling pathway, myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB), regulates BDNF expression in experimental S. pneumoniae meningitis. MyD88 knockout (myd88-/-) mice and wild-type littermates were infected intracisternally with S...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615357/donor-pulmonary-intravascular-nonclassical-monocytes-recruit-recipient-neutrophils-and-mediate-primary-lung-allograft-dysfunction
#19
Zhikun Zheng, Stephen Chiu, Mahzad Akbarpour, Haiying Sun, Paul A Reyfman, Kishore R Anekalla, Hiam Abdala-Valencia, Daphne Edgren, Wenjun Li, Daniel Kreisel, Farida V Korobova, Ramiro Fernandez, Alexandra McQuattie-Pimentel, Zheng J Zhang, Harris Perlman, Alexander V Misharin, G R Scott Budinger, Ankit Bharat
Primary graft dysfunction is the predominant driver of mortality and graft loss after lung transplantation. Recruitment of neutrophils as a result of ischemia-reperfusion injury is thought to cause primary graft dysfunction; however, the mechanisms that regulate neutrophil influx into the injured lung are incompletely understood. We found that donor-derived intravascular nonclassical monocytes (NCMs) are retained in human and murine donor lungs used in transplantation and can be visualized at sites of endothelial injury after reperfusion...
June 14, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28615284/tcl1a-snps-and-estrogen-mediated-toll-like-receptor-myd88-dependent-nf-%C3%AE%C2%BAb-activation-snp-and-serm-dependent-modification-of-inflammation-and-immune-response
#20
Ming-Fen Ho, James N Ingle, Tim Bongartz, Krishna R Kalari, Paul E Goss, Lois E Shepherd, Taisei Mushiroda, Michiaki Kubo, Liewei Wang, Richard M Weinshilboum
In a previous genome-wide association study (GWAS) for musculoskeletal adverse events during aromatase inhibitor therapy of breast cancer, we reported that single nucleotide polymorphisms (SNPs) near the TCL1A gene were associated with this adverse drug reaction. Functional genomic studies showed that TCL1A expression was induced by estradiol (E2), but only in cells with the variant sequence for the top GWAS SNP (rs11849538), a SNP that created a functional estrogen response element. In addition, TCL1A genotype influenced the "downstream" expression of a series of cytokines and chemokines and had a striking effect on NF-κB transcriptional activity...
June 14, 2017: Molecular Pharmacology
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