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https://www.readbyqxmd.com/read/29158420/superoxide-production-by-nadph-oxidase-intensifies-macrophage-antiviral-responses-during-diabetogenic-coxsackievirus-infection
#1
Ashley R Burg, Shaonli Das, Lindsey E Padgett, Zachary E Koenig, Hubert M Tse
Coxsackievirus B infections are suspected environmental triggers of type 1 diabetes (T1D) and macrophage antiviral responses may provide a link to virus-induced T1D. We previously demonstrated an important role for NADPH oxidase (NOX)-derived superoxide production during T1D pathogenesis, as NOX-deficient NOD mice (NOD.Ncf1(m1J) ) were protected against T1D due, in part, to impaired proinflammatory TLR signaling in NOD.Ncf1(m1J) macrophages. Therefore, we hypothesized that loss of NOX-derived superoxide would dampen diabetogenic antiviral macrophage responses and protect from virus-induced diabetes...
November 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29157965/polymer-based-nanoparticles-loaded-with-a-tlr7-ligand-to-target-the-lymph-node-for-immunostimulation
#2
Jérôme Widmer, Cédric Thauvin, Inès Mottas, Van N'guyen, Florence Delie, Eric Allémann, Carole Bourquin
Small-molecule agonists for the Toll-like receptors (TLR) 7 and 8 are effective for the immunotherapy of skin cancer when used as topical agents. Their systemic use has however been largely unsuccessful due to dose-limiting toxicity. We propose a polymer-based nanodelivery system to target resiquimod, a TLR7 ligand, to the lymph node in order to focus the immunostimulatory activity and to prevent a generalized inflammatory response. We demonstrate successful encapsulation of resiquimod in methoxypoly(ethylene glycol)-b-poly(DL-lactic acid) (mPEG-PLA) and mixed poly(DL-lactic-co-glycolic acid) (PLGA)/mPEG-PLA nanoparticles...
November 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29157665/lipopolysaccharide-induced-increase-in-intestinal-epithelial-tight-permeability-is-mediated-by-toll-like-receptor-4-myeloid-differentiation-primary-response-88-myd88-activation-of-myosin-light-chain-kinase-expression
#3
Meghali Nighot, Rana Al-Sadi, Shuhong Guo, Manmeet Rawat, Prashant Nighot, Martin D Watterson, Thomas Y Ma
Lipopolysaccharides (LPSs) are a major component of the Gram-negative bacterial cell wall and play an important role in mediating intestinal inflammatory responses in inflammatory bowel disease. Although recent studies suggested that physiologically relevant concentrations of LPS (0 to 1 ng/mL) cause an increase in intestinal epithelial tight junction (TJ) permeability, the mechanisms that mediate an LPS-induced increase in intestinal TJ permeability remain unclear. Herein, we show that myosin light chain kinase (MLCK) plays a central role in the LPS-induced increase in TJ permeability...
December 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29157306/a-pilot-study-of-the-immunogenicity-of-a-9-peptide-breast-cancer-vaccine-plus-poly-iclc-in-early-stage-breast-cancer
#4
Patrick M Dillon, Gina R Petroni, Mark E Smolkin, David R Brenin, Kimberly A Chianese-Bullock, Kelly T Smith, Walter C Olson, Ibrahim S Fanous, Carmel J Nail, Christiana M Brenin, Emily H Hall, Craig L Slingluff
BACKGROUND: Breast cancer remains a leading cause of cancer death worldwide. There is evidence that immunotherapy may play a role in the eradication of residual disease. Peptide vaccines for immunotherapy are capable of durable immune memory, but vaccines alone have shown sparse clinical activity against breast cancer to date. Toll-like receptor (TLR) agonists and helper peptides are excellent adjuvants for vaccine immunotherapy and they are examined in this human clinical trial. METHODS: A vaccine consisting of 9 MHC class I-restricted breast cancer-associated peptides (from MAGE-A1, -A3, and -A10, CEA, NY-ESO-1, and HER2 proteins) was combined with a TLR3 agonist, poly-ICLC, along with a helper peptide derived from tetanus toxoid...
November 21, 2017: Journal for Immunotherapy of Cancer
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
#5
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
#6
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
#7
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/29155324/angiotensin-receptor-blocker-irbesartan-reduces-stress-induced-intestinal-inflammation-via-at1a-signaling-and-ace2-dependent-mechanism-in-mice
#8
Maimaiti Yisireyili, Yasuhiro Uchida, Koji Yamamoto, Takayuki Nakayama, Xian Wu Cheng, Tadashi Matsushita, Shigeo Nakamura, Toyoaki Murohara, Kyosuke Takeshita
Stress is associated with pathophysiology of both irritable bowel syndrome (IBS) and hypertension. Angiotensin receptor blockers (ARB) have anti-inflammatory properties via inhibition of angiotensin II (Ang II)/Ang II type I receptor axis (AT1). Inhibition of the classical RAS pathway is also involved in upregulation of angiotensin converting enzyme-2 (ACE2), which activates the Ang-(1-7) /Mas pathway to counteract inflammatory signaling and acts as a partner of the amino acid transporter, B(0)AT-1, to absorb tryptophan for regulation of microbiota-gut-brain axis...
November 16, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29155256/role-of-toll-like-receptors-in-inflammatory-bowel-disease
#9
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/29155198/immunomodulating-activity-of-the-polysaccharide-tlh-3from-tricholomalobayense-in-raw264-7-macrophages
#10
Mingzhu Zhang, Xiaohe Tian, Ya Wang, Dandan Wang, Wan Li, Lei Chen, Wenjun Pan, Shomaila Mehmood, Yan Chen
Polysaccharide TLH-3 extracted from Tricholoma lobayense possessed unique antioxidant and anti-aging activities, whereas its immunomodulatory properties remain unexplored. Herein in order to explore TLH-3 biological activities, the immunomodulatory effects on RAW264.7 macrophages and its molecular mechanisms were investigated. It was showed that TLH-3 could significantly enhance the phagocytic activity, releasing toxic molecules NO (nitricoxide), secretion of the cytokine TNF-?(tumor necrosis factor-?, IL-6 (interleukin-6)...
November 16, 2017: International Journal of Biological Macromolecules
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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/29151138/optical-coherence-tomography-guided-percutaneous-coronary-intervention-compared-with-other-imaging-guidance-a-meta-analysis
#17
Kayode O Kuku, Emmanuel Ekanem, Viana Azizi, Gebremedhin Melaku, Anh Bui, Yael F Meirovich, Aaphtaab Dheendsa, Solomon Beyene, Alexandre Hideo-Kajita, Michael J Lipinski, Ron Waksman, Hector M Garcia-Garcia
The use of optical coherence tomography (OCT) in PCI guidance is limited perhaps by the lack of adequately powered studies which compare its efficacy and outcomes to the other more popular imaging modalities. We therefore performed a meta-analysis to compare clinical outcomes following OCT-guided PCI with the other imaging modalities in two separate comparisons. We abstracted data from randomized control trials and observational comparative studies focusing on OCT versus either angiography- or IVUS-guided PCI outcomes identified following a systematic search (April 2006 and May 2017)...
November 18, 2017: International Journal of Cardiovascular Imaging
https://www.readbyqxmd.com/read/29150944/toll-like-receptor-signaling-pathway-as-a-potential-therapeutic-target-in-colorectal-cancer
#18
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
#19
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
#20
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
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