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https://www.readbyqxmd.com/read/28698123/identification-molecular-evolution-of-toll-like-receptors-in-a-tibetan-schizothoracine-fish-gymnocypris-eckloni-and-their-expression-profiles-in-response-to-acute-hypoxia
#1
Delin Qi, Mingzhe Xia, Yan Chao, Yongli Zhao, Rongrong Wu
Hypoxia plays an important role in regulating a variety of physiological responses as well as in pathological situations, but to date the roles of Toll-like receptors (TLRs) in fish in response to hypoxia are still poorly understood. Here, we sequenced the transcriptome of G. eckloni and identified the members of TLR family by scanning transcriptome, and then investigated the expression profiles of a complete set of TLRs in G. eckloni in response to acute hypoxia (4 h at DO = 0.3 ± 0.1 mg/L). The de novo-assembled transcriptome consisted of a total of 162,235 transcripts, further clustered into 110,231 unigenes...
July 8, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28665921/rhododendrin-inhibits-toll-like-receptor-7-mediated-psoriasis-like-skin-inflammation-in-mice
#2
Yoon-Jae Jeon, Shyam Kishor Sah, Hee Seung Yang, Ji Hae Lee, Jongheon Shin, Tae-Yoon Kim
Many active compounds present in Rhododendron brachycarpum have been used in traditional Oriental medicine for the treatment of various skin diseases. However, the precise mechanism of action of the compounds isolated from R. brachycarpum and their relevance as therapeutics for the treatment of psoriasis remain elusive. In this study, we report that rhododendrin isolated from R. brachycarpum strongly inhibits imiquimod (IMQ)-induced psoriasis-like skin inflammation in mice. We showed that topical treatment with rhododendrin reduces IMQ-induced skin hyperplasia, inflammatory mononuclear cell infiltration and the expression of pro-inflammatory mediators in mouse skin...
June 30, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28637878/cd4-t-cell-and-nk-cell-interplay-key-to-regression-of-mhc-class-i-low-tumors-upon-tlr7-8-agonist-therapy
#3
Elien M Doorduijn, Marjolein Sluijter, Daniela C Salvatori, Serenella Silvestri, Saskia Maas, Ramon Arens, Ferry Ossendorp, Sjoerd H van der Burg, Thorbald van Hall
One of the next challenges in cancer immunotherapy is the resistance of tumors to T cell-based treatments through loss of MHC class I. Here, we show that under these circumstances, the Toll-like receptor (TLR)-7/8 ligand imiquimod, but not the TLR3 ligand poly I:C or TLR9 ligand CpG, mediated an effective antitumor response. The rejection of these immune-escaped cancers was mediated by NK cells and CD4(+) T cells, whereas activated CD8(+) T cells were dispensable. Application of the innate immune stimulator at a distant site activated NK cells and thereby elicited tumor-specific T-cell responses in tumor-bearing mice...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28635072/plgf-enhances-tlr-dependent-inflammatory-responses-in-human-mononuclear-phagocytes
#4
Laura F Newell, Shernan G Holtan, Jane E Yates, Leonardo Pereira, Jeffrey W Tyner, Irina Burd, Grover C Bagby
PROBLEM: Levels of placental growth factor (PlGF) peak during third trimester of pregnancy, a time when women are at increased risk of virus-induced morbidity. We hypothesized PlGF might contribute to an exaggerated inflammatory response to Toll-like receptor (TLR) activation. METHOD OF STUDY: Primary human adult and cord blood CD14(+) cells were cultured in the presence of TLR ligands and/or PlGF. RESULTS: PlGF significantly enhanced the magnitude and duration of TNF messenger RNA and protein production by TLR-7/8-activated monocytes, and increased subsequent production of TNF-independent inflammatory cytokines...
June 20, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28609762/increased-toll-like-receptor-myeloid-differentiation-factor-88-expression-at-the-maternal-fetal-interface-is-associated-with-spontaneous-abortion
#5
Mengzhou He, Yuan Zhou, Min Jiang, Fanfan Li, Meitao Yang, Yao Fan, Dongrui Deng
AIMS: Toll-like receptors (TLRs) form a group of pattern recognition receptors that play a major role in maintaining innate host immunity. Myeloid differentiation factor 88 (MyD88) is an adaptor molecule that is essential for signaling via the TLR family. To analyze the mechanism of the imbalance in the innate immune system mediated by TLRs-MyD88 in spontaneous abortion, we detected the expression of TLR-2, TLR-4, TLR-7, and MyD88 in placentae and deciduas. METHODS: The expression of TLR-2, TLR-4, TLR-7, and MyD88 in the placentae and deciduas of abortion-prone mice (n = 10) and normal pregnant mice (n = 10) were analyzed by immunochemistry, western blot, and real-time polymerase chain reaction...
June 14, 2017: Gynecologic and Obstetric Investigation
https://www.readbyqxmd.com/read/28601430/imiquimod-induced-autophagy-is-regulated-by-er-stress-mediated-pkr-activation-in-cancer-cells
#6
Shu-Hao Chang, Shi-Wei Huang, Sin-Ting Wang, Kai-Cheng Chung, Chia-Wei Hsieh, Jun-Kai Kao, Yi-Ju Chen, Chun-Ying Wu, Jeng-Jer Shieh
BACKGROUND: Autophagy is a highly conserved cellular catabolic pathway for degradation and recycling of intracellular components in response to nutrient starvation or environmental stress. Endoplasmic reticulum (ER) homeostasis can be disturbed by physiological and pathological influences, resulting in accumulation of misfolded and unfolded proteins in the ER lumen, a condition referred to as ER stress. Imiquimod (IMQ), a Toll-like receptor (TLR) 7 ligand, possesses anti-tumor and anti-viral activities in vitro and in vivo...
May 2, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28591543/influence-of-polyphenol-rich-diet-on-exercise-induced-immunomodulation-in-male-endurance-athletes
#7
Korbinian Lackermair, Johannes Scherr, Georg Waidhauser, Heiko Methe, Eva Hoster, David C Nieman, Alan Hanley, Sebastian Clauss, Martin Halle, Thomas Nickel
<u>Introduction:</u> Stress is associated with increased susceptibility to infection. We investigated if the mechanism involves immunomodulation of dendritic cells and whether this can be inhibited by a polyphenol-rich diet. <u>Methods:</u> Blood samples were taken from a total of 100 male endurance athletes at five time points around a marathon run: four weeks before, during one week before, and immediately, 24hours and 72hours after. Participants were randomized into two double blinded groups...
June 7, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28580131/recent-insights-into-the-implications-of-metabolism-in-plasmacytoid-dendritic-cell-innate-functions-potential-ways-to-control-these-functions
#8
REVIEW
Philippe Saas, Alexis Varin, Sylvain Perruche, Adam Ceroi
There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC), another type of innate immune cells. These cells are the main type I interferon (IFN) producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6) or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β)...
2017: F1000Research
https://www.readbyqxmd.com/read/28572564/plasmacytoid-dendritic-cells-appear-inactive-during-sub-microscopic-plasmodium-falciparum-blood-stage-infection-yet-retain-their-ability-to-respond-to-tlr-stimulation
#9
Jessica R Loughland, Gabriela Minigo, Derek S Sarovich, Matt Field, Peta E Tipping, Marcela Montes de Oca, Kim A Piera, Fiona H Amante, Bridget E Barber, Matthew J Grigg, Timothy William, Michael F Good, Denise L Doolan, Christian R Engwerda, Nicholas M Anstey, James S McCarthy, Tonia Woodberry
Plasmacytoid dendritic cells (pDC) are activators of innate and adaptive immune responses that express HLA-DR, toll-like receptor (TLR) 7, TLR9 and produce type I interferons. The role of human pDC in malaria remains poorly characterised. pDC activation and cytokine production were assessed in 59 malaria-naive volunteers during experimental infection with 150 or 1,800 P. falciparum-parasitized red blood cells. Using RNA sequencing, longitudinal changes in pDC gene expression were examined in five adults before and at peak-infection...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28555259/in-vitro-differentiated-plasmacytoid-dendritic-cells-as-a-tool-to-induce-anti-leukemia-activity-of-natural-killer-cells
#10
Yildian Díaz-Rodríguez, Paulo Cordeiro, Assila Belounis, Sabine Herblot, Michel Duval
Acute lymphoblastic leukemia (ALL) is believed to be resistant to NK cell-mediated killing. To overcome this resistance, we developed an innovative approach based on NK cell stimulation with Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC). The translation of this approach into the clinic requires the production of high numbers of human pDC. Herein, we show that in vitro differentiation of cord blood CD34(+) progenitors in the presence of aryl hydrocarbon receptor antagonists gives rise to clinically relevant numbers of pDC, as about 10(8) pDC can be produced from a typical cord blood unit...
May 29, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28543613/comparative-pharmacokinetics-of-acteoside-from-total-glycoside-extracted-from-leaves-of-rehmannia-and-dihuangye-total-glycoside-capsule-in-normal-and-diabetic-nephropathy-rats
#11
Xin-Xin Dai, Shu-Lan Su, Hong-Die Cai, Dan-Dan Wei, Tian-Yao Zheng, Zhen-Hua Zhu, Hui Yan, Er-Xin Shang, Sheng Guo, Da-Wei Qian, Jin-Ao Duan
Rehmannia glutinosa Libosch (RG), is officially listed in the Chinese Pharmacopoeia and is widely used in China. In this paper, a sensitive and rapid ultra-performance liquid chromatography-mass spectrometry method including multiple-reaction monitoring mode was developed and applied to study the pharmacokinetic effect of acteoside from total glycoside extracted from the leaves of Rehmannia (TLR) and Dihuangye total glycoside capsule (DTG) in normal and diabetic nephropathy rats. The diabetic nephropathy rat model was induced by intraperitoneal injection of a small dose of streptozotocin and high-fat diet and plus 5% glucose drinking water...
May 23, 2017: Biomedical Chromatography: BMC
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
#12
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/28474504/mouse-nidovirus-ldv-infection-alleviates-graft-versus-host-disease-and-induces-type-i-ifn-dependent-inhibition-of-dendritic-cells-and-allo-responsive-t-cells
#13
Mélanie Gaignage, Reece G Marillier, Catherine Uyttenhove, Nicolas Dauguet, Anubha Saxena, Bernard Ryffel, Thomas Michiels, Jean-Paul Coutelier, Jacques Van Snick
INTRODUCTION: Viruses have developed multiple mechanisms to alter immune reactions. In 1969, it was reported that lactate dehydrogenase-elevating virus (LDV), a single stranded positive sense mouse nidovirus, delays skin allograft rejection and inhibits spleen alterations in graft versus host disease (GVHD). As the underlying mechanisms have remained unresolved and given the need for new therapies of this disease, we reassessed the effects of the virus on GVHD and tried to uncover its mode of action...
June 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28456734/thermosensitive-gel-based-formulation-for-intratumoral-delivery-of-toll-like-receptor-7-8-dual-agonist-medi9197
#14
Amir Fakhari, Sean Nugent, James Elvecrog, John Vasilakos, Marta Corcoran, Ashenafi Tilahun, Kristen Siebenaler, Jenny Sun, J Anand Subramony, Alexander Schwarz
Toll-like receptor (TLR) agonists TLR 7/8, MEDI9197, is a imidazoquinoline analogue that can be used for cancer immunotherapy based on its efficacy toward a variety of tumors. Systemic administration of TLR agonists results in stimulation of the immune system throughout the entire body causing undesirable side effects. To minimize these adverse events, local administration of TLR agonists including intratumoral (IT) delivery has been introduced. Here, a poloxamer 407 thermogel formulation for IT delivery of a TLR 7/8 dual agonist, MEDI9197, is described in which the combination of the aqueous thermogel and the ethanolic TLR 7/8 dual agonist, MEDI9197, solution leads to precipitated drug particles within the gel...
August 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28429728/a-formulated-tlr7-8-agonist-is-a-flexible-highly-potent-and-effective-adjuvant-for-pandemic-influenza-vaccines
#15
Neal Van Hoeven, Christopher B Fox, Brian Granger, Tara Evers, Sharvari W Joshi, Ghislain I Nana, Sarah C Evans, Susan Lin, Hong Liang, Li Liang, Rie Nakajima, Philip L Felgner, Richard A Bowen, Nicole Marlenee, Airn Hartwig, Susan L Baldwin, Rhea N Coler, Mark Tomai, James Elvecrog, Steven G Reed, Darrick Carter
Since 1997, highly pathogenic avian influenza viruses of the H5N1 subtype have been transmitted from avian hosts to humans. The severity of H5N1 infection in humans, as well as the sporadic nature of H5N1 outbreaks, both geographically and temporally, make generation of an effective vaccine a global public health priority. An effective H5N1 vaccine must ultimately provide protection against viruses from diverse clades. Toll-like receptor (TLR) agonist adjuvant formulations have a demonstrated ability to broaden H5N1 vaccine responses in pre-clinical models...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28406067/rna-and-a-cell-wall-component-of-enterococcus-faecalis-ic-1-are-required-for-phagocytosis-and-interleukin-12-production-by-the-mouse-macrophage-cell-line-j774-1
#16
Junpei Nakase, Yuuichi Ukawa, Syoji Takemoto, Takayoshi Kubo, Yuko M Sagesaka, Ayako Aoki-Yoshida, Mamoru Totsuka
Enterococcus faecalis is a resident lactic acid bacterium in the human intestine. Its immunostimulatory action was reported to be enhanced by heat sterilization. To investigate its beneficial actions, we evaluated the ability of 10 E. faecalis strains to induce interleukin-12 (IL-12) production in a mouse macrophage cell line, J774.1 and found that the strain, E. faecalis IC-1, had a potent IL-12-inducing ability. Furthermore, we investigated the underlying mechanism by treating IC-1 cells with RNase or lysozyme...
June 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28342266/increased-number-of-mast-cells-in-the-dermis-in-actinic-keratosis-lesions-effectively-treated-with-imiquimod
#17
Satomi Oyama, Yoko Funasaka, Shin-Ichi Tsuchiya, Seiji Kawana, Hidehisa Saeki
Actinic keratosis (AK) is a cutaneous cancer in situ which develops as a result of excessive exposure to ultraviolet (UV). Toll-like receptor (TLR)7 agonist imiquimod is a topical immune response modifier and is effective for the treatment of non-melanoma skin cancers. Recently, the diagnostic role of the dermatoscope has been reported in the course of treatment of AK. In addition, mast cells are now considered to contribute to both the innate and adaptive immune systems in topical imiquimod therapy. We assessed the effect of imiquimod treatment by dermatoscopic and immunohistochemical findings in 14 patients with a total of 21 AK lesions...
March 24, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28323387/induction-of-tumor-regression-by-intratumoral-sting-agonists-combined-with-anti-programmed-death-l1-blocking-antibody-in-a-preclinical-squamous-cell-carcinoma-model
#18
Shekhar K Gadkaree, Juan Fu, Rupashree Sen, Michael J Korrer, Clint Allen, Young J Kim
BACKGROUND: Cyclic dinucleotides (CDNs) are bacterial intracellular messengers that have demonstrated antitumor activity in melanoma and breast tumors, although their role in immunotherapy of head and neck squamous cell cancers (HNSCCs) has not been well investigated. METHODS: We measured primary tumor growth rates, mechanism of antitumor activity, and efficacy of programmed death-L1 blockade combinatorial therapy in SCCFVII tumor-bearing C3H/HeOUJ mice undergoing intratumoral injections with RR-cyclic-di-guanine (synthetic CDG), CDG (natural cyclic-di-guanine), R848 (TLR 7/8 agonist), or phosphate buffered saline (PBS, control)...
March 21, 2017: Head & Neck
https://www.readbyqxmd.com/read/28273784/thymosin-%C3%AE-1-expands-deficient-il-10-producing-regulatory-b-cell-subsets-in-relapsing-remitting-multiple-sclerosis-patients
#19
Elena Giacomini, Fabiana Rizzo, Marilena P Etna, Melania Cruciani, Rosella Mechelli, Maria Chiara Buscarinu, Francesca Pica, Cartesio D'Agostini, Marco Salvetti, Eliana M Coccia, Martina Severa
BACKGROUND: B cells are key pathogenic effectors in multiple sclerosis (MS) and several therapies have been designed to restrain B cell abnormalities by directly targeting this lymphocyte population. OBJECTIVES: Moving from our data showing a Toll-like receptor (TLR)7-driven dysregulation of B cell response in relapsing-remitting multiple sclerosis (RRMS) and having found a low serum level of Thymosin-α1 (Tα1) in patients, we investigated whether the addition of this molecule to peripheral blood mononuclear cells (PBMCs) would influence the expansion of regulatory B cell subsets, known to dampen autoimmune inflammation...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28262752/highly-exposed-hiv-1-seronegative-female-commercial-sex-workers-sustain-in-their-genital-mucosa-increased-frequencies-of-tolerogenic-myeloid-and-regulatory-t-cells
#20
V Thibodeau, L Fourcade, A-C Labbé, M Alary, F Guédou, J Poudrier, M Roger
We and others have shown that HIV-1 highly-exposed seronegative (HESN) female commercial sex workers (CSWs) maintain low genital inflammatory conditions to prevent HIV infection. HIV-1 interacts with toll-like receptors (TLR)-7/8 to induce interferon (IFN)-α, an important antiviral and immunomodulatory cytokine, which act together with interleukin (IL)-10, human leukocyte antigen (HLA)-G and immunoglobulin-like transcript (ILT)-4 to initiate a "tolerogenic/regulatory" anti-inflammatory loop. In view of further unravelling elements associated with natural immunity to HIV-1, we have characterised TLR-7, IFN-α, IL-10, HLA-G and ILT-4 expression profiles in the genital tract of female CSWs and HIV-1-uninfected non-CSWs from Benin...
March 6, 2017: Scientific Reports
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