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https://www.readbyqxmd.com/read/29156826/protective-effect-of-ginkgo-biloba-leaves-extract-egb761-on-myocardium-injury-in-ischemia-reperfusion-rats-via-regulation-of-tlr-4-nf-%C3%AE%C2%BAb-signaling-pathway
#1
Yuping Tang, Guisheng Zhou, Lijun Yao, Ping Xue, Danhong Yu, Renjie Xu, Wen Shi, Xin Yao, Zhaowei Yan, Jin-Ao Duan
Beneficial actions of EGb 761 against ischemia/reperfusion (I/R) injury in lung, brain and renal ischemia have been described. However, the relationship between EGb 761 and signal molecules in myocardial ischemia reperfusion has not been well elucidated. In this study, we investigated the effects and mechanism of EGb 761 preconditioning on anti-myocardial I/R injuries in vivo. Meanwhile, their potential anti-oxidative stress and anti-inflammation effect were assessed. Hemodynamic parameters were monitored as left ventricular systolic pressure, LV end-diastolic pressure and maximal rate of increase and decrease of left ventricular pressure (dP/dtmax)...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155869/nf-%C3%AE%C2%BAb-pathways-are-involved-in-m1-polarization-of-raw-264-7-macrophage-by-polyporus-polysaccharide-in-the-tumor-microenvironment
#2
Chun-Ping Liu, Xian Zhang, Qing-Long Tan, Wen-Xing Xu, Chang-Yuan Zhou, Min Luo, Xiong Li, Run-Yue Huang, Xing Zeng
Bladder cancer is one of the most malignant tumors closely associated with macrophages. Polyporus polysaccharide (PPS) has shown excellent efficacy in treating bladder cancer with minimal side effects. However, the molecular mechanisms underlying the effects of PPS in inhibiting bladder cancer remain unclear. In this study, we used macrophages cultured alone or with T24 human bladder cancer cell culture supernatant as study models. We found that PPS enhanced the activities of IFN-γ-stimulated RAW 264.7 macrophages, as shown by the release of inducible nitric oxide synthase (INOS), secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-6, phagocytosis activity, as well as expression of M1 phenotype indicators, such as CD40, CD284 and CD86...
2017: PloS One
https://www.readbyqxmd.com/read/29155428/small-molecule-inhibition-of-tlr8-through-stabilization-of-its-resting-state
#3
Shuting Zhang, Zhenyi Hu, Hiromi Tanji, Shuangshuang Jiang, Nabanita Das, Jing Li, Kentaro Sakaniwa, Jin Jin, Yanyan Bian, Umeharu Ohto, Toshiyuki Shimizu, Hang Yin
Endosomal Toll-like receptors (TLR3, TLR7, TLR8, and TLR9) are highly analogous sensors for various viral or bacterial RNA and DNA molecular patterns. Nonetheless, few small molecules can selectively modulate these TLRs. In this manuscript, we identified the first human TLR8-specific small-molecule antagonists via a novel inhibition mechanism. Crystal structures of two distinct TLR8-ligand complexes validated a unique binding site on the protein-protein interface of the TLR8 homodimer. Upon binding to this new site, the small-molecule ligands stabilize the preformed TLR8 dimer in its resting state, preventing activation...
November 20, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/29155256/role-of-toll-like-receptors-in-inflammatory-bowel-disease
#4
REVIEW
Nastaran Kordjazy, Arvin Haj-Mirzaian, Arya Haj-Mirzaian, Mohammad Mojtaba Rohani, Erwin W Gelfand, Nima Rezaei, Amir Hossein Abdolghaffari
Inflammatory bowel disease (IBD) is the chronic inflammation of the gastrointestinal tract. Recently, studies of the interplay between the adaptive and innate immune responses have provided a better understanding of the immunopathogenesis of inflammatory disorders such as IBD, as well as identification of novel targets for more potent interventions. Toll-like receptors (TLRs) are a class of proteins that play a significant role in the innate immune system and are involved in inflammatory processes. Activation of TLR signal transduction pathways lead to the induction of numerous genes that function in host defense, including those for inflammatory cytokines, chemokines, and antigen presenting molecules...
November 16, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29153953/inhibition-of-curcumin-on-influenza-a-virus-infection-and-influenzal-pneumonia-via-oxidative-stress-tlr2-4-p38-jnk-mapk-and-nf-%C3%AE%C2%BAb-pathways
#5
Jianping Dai, Liming Gu, Yun Su, Qianwen Wang, Ying Zhao, Xiaoxua Chen, Huixiong Deng, Weizhong Li, Gefei Wang, Kangsheng Li
Oxidative stress, Nrf2-HO-1 and TLR-MAPK/NF-κB signaling pathways have been proved to be involved in influenza A virus (IAV) replication and influenzal pneumonia. In the previous studies, we have performed several high-throughput drug screenings based on the TLR pathways. In the present study, through plaque inhibition test, luciferase reporter assay, TCID50, qRT-PCR, western blotting, ELISA and siRNA assays, we investigated the effect and mechanism of action of curcumin against IAV infection in vitro and in vivo...
November 15, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29152585/total-lipopolysaccharide-from-the-human-gut-microbiome-silences-toll-like-receptor-signaling
#6
Eva d'Hennezel, Sahar Abubucker, Leon O Murphy, Thomas W Cullen
Cohabitation of microbial communities with the host enables the formation of a symbiotic relationship that maintains homeostasis in the gut and beyond. One prevailing model suggests that this relationship relies on the capacity of host cells and tissues to remain tolerant to the strong immune stimulation generated by the microbiota such as the activation of Toll-like receptor 4 (TLR4) pathways by lipopolysaccharide (LPS). Indeed, gut microbial LPS is thought to be one of the most potent activators of innate immune signaling and an important mediator of the microbiome's influence on host physiology...
November 2017: MSystems
https://www.readbyqxmd.com/read/29152559/fasciola-hepatica-esps-could-indistinctly-activate-or-block-multiple-toll-like-receptors-in-a-human-monocyte-cell-line
#7
Olgary Figueroa-Santiago, Ana M Espino
Fasciola hepatica is a parasitic helminth that induces Th2/Treg responses in its mammalian host. Some reports have suggested that ESPs achieve these polarized immune responses by delaying the activation of dendritic cells and macrophages during the early stages of innate immunity, a process that is mediated by TLR4. The present study aimed to investigate whether TLRs other than TLR4 could also be targeted by F. hepatica ESPs. To achieve this aim a screening system was optimized using THP1-Blue CD14 cells. ESPs were first separated based on their molecular weight and according their net charge by ion exchange chromatography (IEC)...
2017: Ann Clin Pathol
https://www.readbyqxmd.com/read/29152461/use-of-toll-like-receptor-assays-for-the-detection-of-bacterial-contaminations-in-icodextrin-batches-released-for-peritoneal-dialysis
#8
Hêla Hacine-Gherbi, Agnès Denys, Mathieu Carpentier, Arnaud Heysen, Pierrick Duflot, Pierre Lanos, Fabrice Allain
Icodextrin is a starch derivative used for preparing solutions of peritoneal dialysis. Unfortunately, peptidoglycans (PGN) and lipopolysaccharides (LPS) have been reported to contaminate certain icodextrin batches and to contribute to the development of sterile peritonitis. The decision of selecting or rejecting icodextrin batches is however difficult, because of limitations in the detection of these bacterial contaminants. Besides monocyte activation tests of cytokine release, a number of bio-assays using stably TLR-transfected cell lines have been developed...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/29152046/design-and-synthesis-of-n1-modified-imidazoquinoline-agonists-for-selective-activation-of-toll-like-receptors-7-and-8
#9
Peter Larson, Tamara A Kucaba, Zhengming Xiong, Michael Olin, Thomas S Griffith, David M Ferguson
A series of N1-modified imidazoquinolines were synthesized and screened for Toll-like receptors (TLR) 7 and 8 activities to identify recognition elements that confer high affinity binding and selectivity. These receptors are key targets in the development of immunomodulatory agents that signal the NF-κB mediated transcription of pro-inflammatory chemokines and cytokines. Results are presented showing both TLR7/8 activations are highly correlated to N1-substitution, with TLR8 selectivity achieved through inclusion of an ethyl-, propyl-, or butylamino group at this position...
November 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29151895/toll-like-receptor-4-differentially-mediates-intestinal-and-extra-intestinal-immune-responses-upon-multi-drug-resistant-pseudomonas-aeruginosa-association-of-il10-mice-with-chronic-colitis
#10
Anne Grunau, Ulrike Escher, Anja A Kühl, Stefan Bereswill, Markus M Heimesaat
Background: Infections with multi-drug resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa (PA) have become a serious threat particularly in hospitalized patients with immunopathological co-morbidities. The well-balanced interplay between immune cells, pattern recognition receptors such as Toll-like receptor (TLR)-4 sensing lipopolysaccharide from Gram-negative bacteria including PA, and evolving pathways is crucial to prevent the host from invading (opportunistic) pathogens...
2017: Gut Pathogens
https://www.readbyqxmd.com/read/29150944/toll-like-receptor-signaling-pathway-as-a-potential-therapeutic-target-in-colorectal-cancer
#11
REVIEW
Reyhaneh Moradi-Marjaneh, Seyed Mahdi Hassanian, Hamid Fiuji, Saman Soleimanpour, Gordon A Ferns, Amir Avan, Majid Khazaei
Toll like receptor (TLR) signaling is involved in activating innate and adaptive immune responses and plays a critical role in inflammation-induced diseases such as colorectal cancer (CRC). Dysregulation of this signaling pathway can result in disturbance of epithelial layer hemostasis, chronic inflammatory, excessive repair responses and development of CRC. There is now substantial evidence for the benefit of targeting of this pathway in cancer treatment, and several agents have been approved, such as BCG (Bacillus Calmette Guérin), MPL (monophosphoryl lipid A) and imiquimod...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150600/mapping-tenascin-c-interaction-with-toll-like-receptor-4-reveals-a-new-subset-of-endogenous-inflammatory-triggers
#12
Lorena Zuliani-Alvarez, Anna M Marzeda, Claire Deligne, Anja Schwenzer, Fiona E McCann, Brian D Marsden, Anna M Piccinini, Kim S Midwood
Pattern recognition underpins innate immunity; the accurate identification of danger, including infection, injury, or tumor, is key to an appropriately targeted immune response. Pathogen detection is increasingly well defined mechanistically, but the discrimination of endogenous inflammatory triggers remains unclear. Tenascin-C, a matrix protein induced upon tissue damage and expressed by tumors, activates toll-like receptor 4 (TLR4)-mediated sterile inflammation. Here we map three sites within tenascin-C that directly and cooperatively interact with TLR4...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29150567/amplifying-ifn-%C3%AE-signaling-in-dendritic-cells-by-cd11c-specific-loss-of-socs1-increases-innate-immunity-to-infection-while-decreasing-adaptive-immunity
#13
Alejandro F Alice, Gwen Kramer, Shelly Bambina, Jason R Baird, Keith S Bahjat, Michael J Gough, Marka R Crittenden
Although prophylactic vaccines provide protective humoral immunity against infectious agents, vaccines that elicit potent CD8 T cell responses are valuable tools to shape and drive cellular immunity against cancer and intracellular infection. In particular, IFN-γ-polarized cytotoxic CD8 T cell immunity is considered optimal for protective immunity against intracellular Ags. Suppressor of cytokine signaling (SOCS)1 is a cross-functional negative regulator of TLR and cytokine receptor signaling via degradation of the receptor-signaling complex...
November 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29150563/nfat5-regulated-macrophage-polarization-supports-the-proinflammatory-function-of-macrophages-and-t-lymphocytes
#14
Mónica Tellechea, Maria Buxadé, Sonia Tejedor, Jose Aramburu, Cristina López-Rodríguez
Macrophages are exquisite sensors of tissue homeostasis that can rapidly switch between pro- and anti-inflammatory or regulatory modes to respond to perturbations in their microenvironment. This functional plasticity involves a precise orchestration of gene expression patterns whose transcriptional regulators have not been fully characterized. We had previously identified the transcription factor NFAT5 as an activator of TLR-induced responses, and in this study we explore its contribution to macrophage functions in different polarization settings...
November 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29150239/tissue-resident-macrophages-are-locally-programmed-for-silent-clearance-of-apoptotic-cells
#15
Allison W Roberts, Bettina L Lee, Jacques Deguine, Shinu John, Mark J Shlomchik, Gregory M Barton
Although apoptotic cells (ACs) contain nucleic acids that can be recognized by Toll-like receptors (TLRs), engulfment of ACs does not initiate inflammation in healthy organisms. Here we identified macrophage populations that continually engulf ACs in distinct tissues and found that these macrophages share characteristics compatible with immunologically silent clearance of ACs; such characteristics include high expression of AC recognition receptors, low expression of TLR9, and reduced TLR responsiveness to nucleic acids...
November 13, 2017: Immunity
https://www.readbyqxmd.com/read/29150086/the-ex-vivo-toll-like-receptor-7-tolerance-induction-in-donor-lymphocytes-prevents-murine-acute-graft-versus-host-disease
#16
Nikolaos Zogas, Garyfalia Karponi, Fotios Iordanidis, Stylianos Malasidis, Vasilios Paraskevas, Anastasia Papadopoulou, Zaharias George Scouras, Achilles Anagnostopoulos, Evangelia Yannaki
BACKGROUND AIMS: Acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation, mediated by alloreactive donor T cells. Toll-like receptors (TLRs), a family of conserved pattern-recognition receptors (PRRs), represent key players in donors' T-cell activation during aGVHD; however, a regulatory, tolerogenic role for certain TLRs has been recognized in a different context. We investigated whether the ex vivo-induced TLR-2,-4,-7 tolerance in donor cells could prevent alloreactivity in a mismatched transplantation model...
November 14, 2017: Cytotherapy
https://www.readbyqxmd.com/read/29147820/cue-signal-response-analysis-in-3d-chondrocyte-scaffolds-with-anabolic-stimuli
#17
Michael Neidlin, Antonion Korcari, Giorgos Macheras, Leonidas G Alexopoulos
Articular cartilage is an avascular connective tissue responsible for bearing loads. Cell signaling plays a central role in cartilage homeostasis and tissue engineering by directing chondrocytes to synthesize/degrade the extracellular matrix or promote inflammatory responses. The aim of this paper was to investigate anabolic, catabolic and inflammatory pathways of well-known and underreported anabolic stimuli in 3D chondrocyte cultures and connect them to diverse cartilage responses including matrix regeneration and cell communication...
November 16, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29147012/piperidylmethyloxychalcone-improves-immune-mediated-acute-liver-failure-via-inhibiting-tak1-activity
#18
Sun Hong Park, Jeong-Ah Kwak, Sang-Hun Jung, Byeongwoo Ahn, Won-Jea Cho, Cheong-Yong Yun, Chang Seon Na, Bang Yeon Hwang, Jin Tae Hong, Sang-Bae Han, Youngsoo Kim
Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF...
November 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29146546/signaling-via-toll-like-receptor-4-and-cd40-in-b-cells-plays-a-regulatory-role-in-the-pathogenesis-of-multiple-sclerosis-through-interleukin-10-production
#19
Yoichiro Okada, Hirofumi Ochi, Chihiro Fujii, Yuichiro Hashi, Mio Hamatani, Shinji Ashida, Kazuyuki Kawamura, Hirofumi Kusaka, Sadayuki Matsumoto, Masanori Nakagawa, Toshiki Mizuno, Ryosuke Takahashi, Takayuki Kondo
BACKGROUND: B cells play an important role in the development of multiple sclerosis (MS), but can also exhibit regulatory functions through IL-10 production. Toll-like receptors (TLR) and CD40 signaling are likely to be involved in this process. OBJECTIVE: To investigate the ability of MS B cells to produce IL-10 in response to TLR stimulation in the presence or absence of CD40 co-stimulation. METHODS: Peripheral blood mononuclear cells obtained from 34 MS patients and 24 matched healthy participants (HS) were stimulated through either TLR4 or TLR9 alone, or together with CD40...
November 13, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29144391/antimicrobial-peptide-epinecidin-1-modulates-myd88-protein-levels-via-the-proteasome-degradation-pathway
#20
Bor-Chyuan Su, Jyh-Yih Chen
The cationic antimicrobial peptide epinecidin-1 was identified from Epinephelus coioides and possesses multiple biological functions, including antibacterial, antifungal, anti-tumor, and immunomodulatory effects. In addition, epinecidin-1 suppresses lipopolysaccharide (LPS)-induced inflammation by neutralizing LPS and ameliorating LPS/Toll-like receptor (TLR)-4 internalization. However, it is unclear whether the actions of epinecidin-1 depend on the regulation of TLR adaptor protein MyD88 or endogenous TLR signaling antagonists, which include A20, interleukin-1 receptor associated kinase (IRAK)-M, and suppressor of cytokine signaling (SOCS)-1...
November 16, 2017: Marine Drugs
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