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https://www.readbyqxmd.com/read/28544973/pegylation-of-a-tlr2-agonist-based-vaccine-delivery-system-improves-antigen-trafficking-and-the-magnitude-of-ensuing-antibody-and-cd8-t-cell-responses
#1
Toshiki Sekiya, Junya Yamagishi, John Henry V Gray, Paul G Whitney, Axel Martinelli, Weiguang Zeng, Chinn Yi Wong, Chihiro Sugimoto, David C Jackson, Brendon Y Chua
The lipopeptide R4Pam2Cys is an agonist for toll-like receptor-2 (TLR2), a key pathogen-associated molecular pattern receptor expressed on many antigen-presenting cells such as dendritic cells (DCs). Electrostatic association of R4Pam2Cys with soluble protein antigens significantly enhances their immunogenicity and there is evidence to suggest that reducing the size of suitably adjuvanted-antigen complexes in solution may further improve their immunostimulatory capabilities. In this study, we investigated how incorporation of polyethylene glycol (PEG) into R4Pam2Cys affects the size, activity and efficacy of formed antigen-lipopeptide complexes...
May 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28544543/acute-toll-like-receptor-4-activation-impairs-rat-renal-microvascular-autoregulatory-behaviour
#2
Justin P Van Beusecum, Shali Zhang, Anthony K Cook, Edward W Inscho
AIM: Little is known about how toll-like receptor 4 (TLR4) influences the renal microvasculature. We hypothesized that acute TLR4 stimulation with lipopolysaccharide (LPS) impairs afferent arteriole autoregulatory behaviour, partially through reactive oxygen species (ROS). METHODS: We assessed afferent arteriole autoregulatory behaviour after LPS treatment (1 mg kg(-1) ; i.p.) using the in vitro blood perfused juxtamedullary nephron preparation. Autoregulatory behaviour was assessed by measuring diameter responses to step-wise changes in renal perfusion pressure...
May 25, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28544067/vitamin-d3-alters-the-expression-of-toll-like-receptors-in-peripheral-blood-mononuclear-cells-of-patients-with-systemic-lupus-erythematosus
#3
Esmaeil Yazdanpanah, Mahmoud Mahmoudi, Maryam Sahebari, Zahra Rezaieyazdi, Seyed-Alireza Esmaeili, Nafiseh Tabasi, Soheila Jaberi, Amirhossein Sahebkar, Maryam Rastin
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by production of inflammatory cytokines and autoreactive antibodies due to the loss of immune tolerance. Recognition of self-nucleic acids by intracellular Toll-like receptors (TLRs) can overactivate immune responses and this abnormal activation of TLRs contributes to the pathogenesis of the disease. In recent years, anti-inflammatory and immunomodulatory effects of 1, 25-dihydroxyvitamin D3 (VitD3) on the immune system has received particular attention...
May 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28543911/polymorphism-of-tlr5-rs5744174-is-associated-with-disease-progression-in-chinese-patients-with-chronic-hbv-infection
#4
Lina Cao, Tong Zhang, Junping Zhu, Aixin Li, Kai Zheng, Nan Zhang, Bin Su, Wei Xia, Hao Wu, Ning Li, Qiushui He
Toll-like receptors (TLRs) play a crucial role in innate and adaptive immunity, protecting the host from viral pathogens. Studies have implicated that TLR5 is associated with various diseases such as autoimmune and inflammation related diseases. However, little is known about the relationship between TLR5 and hepatitis B virus (HBV) infection. We studied the effect of TLR5 gene polymorphisms on susceptibility to and disease progression of chronic hepatitis B (CHB) infection in Chinese. Blood samples were taken from 636 patients with CHB, HBV-related liver cirrhosis (LC) or hepatocellular carcinoma (HCC) and 273 controls...
May 25, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28543180/traf6-participates-in-early-brain-injury-after-subarachnoid-hemorrhage-in-rats-through-inhibiting-autophagy-and-promoting-oxidative-stress
#5
Yang Dou, Haitao Shen, Dongxia Feng, Haiying Li, Xiaodi Tian, Jian Zhang, Zhong Wang, Gang Chen
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a member of the TRAF family and an important multifunctional intracellular adaptin of the tumor necrosis factor (TNF) superfamily and toll/IL-1 receptor (TIR) superfamily. TRAF6 has been studied in several central nervous system (CNS) diseases, including ischemic stroke, traumatic brain injury and neurodegenerative diseases, but its role in subarachnoid hemorrhage (SAH) has not been fully illustrated. This study was designed to explore changes of expression level and potential roles and mechanisms of TRAF6 in early brain injury (EBI) after SAH by using a Sprague-Dawley rat model of SAH induced in 0...
May 24, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28542588/inhibition-of-hmgb1-protects-the-retina-from-ischemia-reperfusion-as-well-as-reduces-insulin-resistance-proteins
#6
Li Liu, Youde Jiang, Jena J Steinle
The role of inflammation in diabetic retinal amage is well accepted. While a number of cytokines and inflammatory mediators are responsible for these changes, upstream regulators are less well studied. Additionally, the role for these upstream mediators in retinal health is unclear. In this study, we hypothesized that inhibition of high mobility group box 1 (HMGB1) could restore normal insulin signaling in retinal endothelial cells (REC) grown in high glucose, as well as protect the retina against ischemia/reperfusion (I/R)-induced retinal damage...
2017: PloS One
https://www.readbyqxmd.com/read/28542462/a-human-monocytic-nf-%C3%AE%C2%BAb-fluorescent-reporter-cell-line-for-detection-of-microbial-contaminants-in-biological-samples
#7
Claire Battin, Annika Hennig, Patrick Mayrhofer, Renate Kunert, Gerhard J Zlabinger, Peter Steinberger, Wolfgang Paster
Sensing of pathogens by innate immune cells is essential for the initiation of appropriate immune responses. Toll-like receptors (TLRs), which are highly sensitive for various structurally and evolutionary conserved molecules derived from microbes have a prominent role in this process. TLR engagement results in the activation of the transcription factor NF-κB, which induces the expression of cytokines and other inflammatory mediators. The exquisite sensitivity of TLR signalling can be exploited for the detection of bacteria and microbial contaminants in tissue cultures and in protein preparations...
2017: PloS One
https://www.readbyqxmd.com/read/28542370/upregulation-of-tlr4-via-pkc-activation-contributes-to-impaired-wound-healing-in-high-glucose-treated-kidney-proximal-tubular-cells
#8
Jianping Peng, Hang Zheng, Xia Wang, Zhixiang Cheng
Acute kidney injury (AKI) leads to a worse prognosis in diabetic patients compared with prognoses in non-diabetic patients, but whether and how diabetes affects kidney repair after AKI remains unknown. Here, we used scratch-wound healing and transwell migration models to examine whether and how wound healing is affected by high glucose levels in cultured kidney proximal tubular cells (RPTC). The results show that scratch-wound healing and transwell migration were significantly slower in high-glucose-treated kidney tubular cells (30 mM glucose) than in low-glucose-treated cells (5...
2017: PloS One
https://www.readbyqxmd.com/read/28542326/the-murine-cytomegalovirus-m35-protein-antagonizes-type-i-ifn-induction-downstream-of-pattern-recognition-receptors-by-targeting-nf-%C3%AE%C2%BAb-mediated-transcription
#9
Baca Chan, Vladimir Gonçalves Magalhães, Niels A W Lemmermann, Vanda Juranić Lisnić, Markus Stempel, Kendra A Bussey, Elisa Reimer, Jürgen Podlech, Stefan Lienenklaus, Matthias J Reddehase, Stipan Jonjić, Melanie M Brinkmann
The type I interferon (IFN) response is imperative for the establishment of the early antiviral immune response. Here we report the identification of the first type I IFN antagonist encoded by murine cytomegalovirus (MCMV) that shuts down signaling following pattern recognition receptor (PRR) sensing. Screening of an MCMV open reading frame (ORF) library identified M35 as a novel and strong negative modulator of IFNβ promoter induction following activation of both RNA and DNA cytoplasmic PRR. Additionally, M35 inhibits the proinflammatory cytokine response downstream of Toll-like receptors (TLR)...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542251/transcriptome-microrna-analysis-of-sarcoptes-scabiei-and-host-immune-response
#10
Ran He, Xiaobin Gu, Weimin Lai, Xuerong Peng, Guangyou Yang
Scabies is a parasitic disease, caused by the mite Sarcoptes scabiei, and is considered one of the top 50 epidemic diseases and one the most common human skin disease, worldwide. Allergic dermatitis, including an intense itch, is a common symptom, however diagnosis is difficult and there is currently no effective vaccine. The goal of this study was to examine the immune interaction mechanism of both S. scabiei and infected hosts. mRNA-seq and microRNA-seq were conducted on the S. scabiei mite and on infected and uninfected hosts...
2017: PloS One
https://www.readbyqxmd.com/read/28542146/the-role-of-extracellular-histone-in-organ-injury
#11
REVIEW
Eleanor Silk, Hailin Zhao, Hao Weng, Daqing Ma
Histones are intra-nuclear cationic proteins that are present in all eukaryotic cells and are highly conserved across species. Within the nucleus, they provide structural stability to chromatin and regulate gene expression. Histone may be released into the extracellular space in three forms: freely, as a DNA-bound nucleosome or as part of neutrophil extracellular traps, and all three can be detected in serum after significant cellular death such as sepsis, trauma, ischaemia/reperfusion injury and autoimmune disease...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28541576/rapidly-evolving-toll-3-4-genes-encode-male-specific-toll-like-receptors-in-drosophila
#12
Tera C Levin, Harmit S Malik
Animal Toll-like receptors (TLRs) have evolved through a pattern of duplication and divergence. Whereas mammalian TLRs directly recognize microbial ligands, Drosophila Tolls bind endogenous ligands downstream of both developmental and immune signaling cascades. Here, we find that most Toll genes in Drosophila evolve slowly with little gene turnover (gains/losses), consistent with their important roles in development and indirect roles in microbial recognition. In contrast, we find that the Toll-3/4 genes have experienced an unusually rapid rate of gene gains and losses, resulting in lineage-specific Toll-3/4s and vastly different gene repertoires among Drosophila species, from zero copies (e...
May 25, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28540671/multidisciplinary-management-of-mycosis-fungoides-s%C3%A3-zary-syndrome
#13
REVIEW
Sara Berg, Jennifer Villasenor-Park, Paul Haun, Ellen J Kim
PURPOSE OF REVIEW: Diagnosis and management of mycosis fungoides and Sézary syndrome (MF/SS) require accurate clinicopathological correlation and a multidisciplinary approach. We reviewed major advances in the field regarding diagnostic and prognostic tools as well as skin-directed therapies (SDTs) and systemic agents for MF/SS published in the past 2 years. RECENT FINDINGS: Improved technology (T-cell receptor high-throughput sequencing) and increased multicenter collaboration (Cutaneous Lymphoma International Consortium) have led to diagnostic/prognostic advances...
May 24, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28539706/multiple-immunosuppressive-effects-of-cpg-c41-on-intracellular-tlr-mediated-inflammation
#14
Wancheng Liu, Xuejiao Yang, Ning Wang, Shijun Fan, Yuanfeng Zhu, Xinchuan Zheng, Yan Li
A growing body of literature suggests that most chronic autoimmune diseases are associated with inappropriate inflammation mediated by Toll-like receptor (TLR) 3, TLR7/8, or TLR9. Therefore, research into blocking TLR activation to treat these disorders has become a hot topic. Here, we report the immunomodulatory properties of a nonstimulatory CpG-containing oligodeoxynucleotide (CpG-ODN), CpG-c41, which had previously only been known as a TLR9 antagonist. In this study, we found that both in vitro and in vivo CpG-c41 decreased levels of various proinflammatory factors that were induced by single activation or coactivation of intracellular TLRs, but not membrane-bound TLRs, no matter what downstream signal pathways the TLRs depend on...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28539639/the-absence-of-interferon-%C3%AE-promotor-stimulator-1-ips-1-predisposes-to-bronchiolitis-and-asthma-like-pathology-in-response-to-pneumoviral-infection-in-mice
#15
Jennifer Simpson, Jason P Lynch, Zhixuan Loh, Vivian Zhang, Rhiannon B Werder, Kirsten Spann, Simon Phipps
Respiratory syncytial virus (RSV)-bronchiolitis is a major cause of infant morbidity and mortality and a risk factor for subsequent asthma. We showed previously that toll-like receptor (TLR)7 in plasmacytoid dendritic cells (pDCs) is critical for protection against bronchiolitis and asthma in mice infected with pneumonia virus of mice (PVM), the mouse homolog of RSV. This lack of redundancy was unexpected as interferon-β promotor stimulator-1 (IPS-1) signalling, downstream of RIG-I-like receptor (RLR) and not TLR7 activation, contributes to host defence in hRSV-inoculated adult mice...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539262/synthetic-anti-endotoxin-peptides-inhibit-cytoplasmic-lps-mediated-responses
#16
Anja Pfalzgraff, Lena Heinbockel, Qi Su, Klaus Brandenburg, Günther Weindl
Toll-like receptor (TLR) 4-independent recognition of lipopolysaccharide (LPS) in the cytosol by inflammatory caspases leads to non-canonical inflammasome activation and induction of IL-1 secretion and pyroptosis. The discovery of this novel mechanism has potential implications for the development of effective drugs to treat sepsis since LPS-mediated hyperactivation of caspases is critically involved in endotoxic shock. Previously, we demonstrated that Pep19-2.5, a synthetic anti-endotoxin peptide, efficiently neutralises pathogenicity factors of Gram-negative and Gram-positive bacteria and protects against sepsis in vivo...
May 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28538192/hepatic-anti-inflammatory-effect-of-hexane-extracts-of-dioscorea-batatas-decne-possible-suppression-of-toll-like-receptor-4-mediated-signaling
#17
Hyun Jung Koo, SungRyul Lee, Kwang Jin Chang, Eunsoo Sohn, Eun-Hwa Sohn, Se Chan Kang, Suhkneung Pyo
The hepatic anti-inflammatory potential of hexane extracts of Dioscorea batatas Decne edible part (EDH-1e) and bark (EDH-2b) were investigated in Western-type diet-fed apolipoprotein E null [ApoE (-/-)] mice and HepG2 cells. EDH-1e and EDH-2b suppressed the increased levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, transforming growth factor beta 1 (TGF-β1), vascular cell adhesion protein 1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1), and reduced infiltration of monocytes into liver tissue...
May 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28538085/circulating-heparan-sulfate-fragments-attenuate-histone-induced-lung-injury-independently-of-histone-binding
#18
Yanlin Zhang, Sarah M Haeger, Yimu Yang, Kyrie L Dailey, Joshay A Ford, Eric P Schmidt
Extracellular histones are cationic damage-associated molecular pattern molecules capable of directly inducing cellular injury via charge-mediated interactions with plasma membranes. Accordingly, histones released into the plasma during critical illness are known to contribute to the onset and propagation of lung injury. Vascular injury (with consequent degradation of the endothelial glycocalyx) simultaneously releases anionic heparan sulfate fragments (hexa- to octasaccharides in size) into the plasma. It is unknown whether this endogenous release of heparan sulfate fragments modulates charge-dependent histone cytotoxicity, or if exogenous heparan sulfate fragments could therapeutically attenuate histone-induced lung injury...
May 23, 2017: Shock
https://www.readbyqxmd.com/read/28537730/discovery-of-small-molecules-as-multi-toll-like-receptor-agonists-with-proinflammatory-and-anticancer-activities
#19
Lei Zhang, Varun Dewan, Hang Hubert Yin
Therapies based on activation of multiple Toll-like receptors (TLRs) may offer superior therapeutic profiles than that of single TLR activation. To discover new small molecules that could activate multiple TLRs, we performed a cell-based high-throughput screening of a small-molecule library based on TLR3-mediated NF-κB activation. Subsequent structural optimization and counter screening of other TLRs produced the first small molecule (CU-CPT24e) capable of simultaneously activating TLRs 3, 8, and 9. Biochemical studies demonstrated that CU-CPT24e could induce a strong immune response via the production of various cytokines in human monocytic THP-1 cells...
May 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28537664/study-on-the-expression-of-toll-like-receptor-4-and-matrix-metalloproteinase-9-in-patients-with-chronic-obstructive-pulmonary-disease-and-their-clinical-significance
#20
Y Zhang, H-J Ni, H-S Zhou
OBJECTIVE: To investigate the expression of Toll-like receptor 4 (TLR4) and matrix metalloproteinase-9 (MMP-9) in patients with chronic obstructive pulmonary disease (COPD) and their clinical significance. PATIENTS AND METHODS: Paracancerous tissues from 48 patients with lung squamous cell carcinoma harvested during pulmonary lobectomy were studied. Twenty-four cases of COPD were chosen as the observation group and 24 cases of non-COPD as the control group. The degree of lung inflammation was observed; the ratio of the thickness of the wall to the external diameter of the pulmonary arterioles (WT%), and the ratio of the area of the wall to that of the pulmonary arterioles (WA%) were calculated...
May 2017: European Review for Medical and Pharmacological Sciences
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