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https://www.readbyqxmd.com/read/28212561/the-tlr7-agonist-imiquimod-induces-anti-cancer-effects-via-autophagic-cell-death-and-enhances-anti-tumoral-and-systemic-immunity-during-radiotherapy-for-melanoma
#1
Jeong Hyun Cho, Hyo-Ji Lee, Hyun-Jeong Ko, Byung-Il Yoon, Jongseon Choe, Keun-Cheol Kim, Tae-Wook Hahn, Jeong A Han, Sun Shim Choi, Young Mee Jung, Kee-Ho Lee, Yun-Sil Lee, Yu-Jin Jung
Toll-like receptor (TLR) ligands are strongly considered immune-adjuvants for cancer immunotherapy and have been shown to exert direct anti-cancer effects. This study was performed to evaluate the synergistic anti-cancer and anti-metastatic effects of the TLR7 agonist imiquimod (IMQ) during radiotherapy for melanoma. The pretreatment of B16F10 or B16F1 cells with IMQ combined with γ-ionizing radiation (IR) led to enhanced cell death via autophagy, as demonstrated by increased expression levels of autophagy-related genes, and an increased number of autophagosomes in both cell lines...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212352/rta-occupancy-of-the-origin-of-lytic-replication-during-murine-gammaherpesvirus-68-reactivation-from-b-cell-latency
#2
Alexis L Santana, Darby G Oldenburg, Varvara Kirillov, Laraib Malik, Qiwen Dong, Roman Sinayev, Kenneth B Marcu, Douglas W White, Laurie T Krug
RTA, the viral Replication and Transcription Activator, is essential for rhadinovirus lytic gene expression upon de novo infection and reactivation from latency. Lipopolysaccharide (LPS)/toll-like receptor (TLR)4 engagement enhances rhadinovirus reactivation. We developed two new systems to examine the interaction of RTA with host NF-kappaB (NF-κB) signaling during murine gammaherpesvirus 68 (MHV68) infection: a latent B cell line (HE-RIT) inducible for RTA-Flag expression and virus reactivation; and a recombinant virus (MHV68-RTA-Bio) that enabled in vivo biotinylation of RTA in BirA transgenic mice...
February 16, 2017: Pathogens
https://www.readbyqxmd.com/read/28211536/expression-profiling-of-trim-protein-family-in-thp1-derived-macrophages-following-tlr-stimulation
#3
Mei-Xiu Jiang, Xuan Hong, Bin-Bin Liao, Shui-Zhen Shi, Xiao-Fang Lai, Huai-Yu Zheng, Lin Xie, Yuan Wang, Xiao-Lei Wang, Hong-Bo Xin, Mingui Fu, Ke-Yu Deng
Activated macrophages play an important role in many inflammatory diseases including septic shock and atherosclerosis. However, the molecular mechanisms limiting macrophage activation are not completely understood. Members of the tripartite motif (TRIM) family have recently emerged as important players in innate immunity and antivirus. Here, we systematically analyzed mRNA expressions of representative TRIM molecules in human THP1-derived macrophages activated by different toll-like receptor (TLR) ligands. Twenty-nine TRIM members were highly induced (>3 fold) by one or more TLR ligands, among which 19 of them belong to TRIM C-IV subgroup...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28210837/toll-like-receptor-3-tlr-3-tlr-4-and-cd80-expression-in-peripheral-blood-mononuclear-cells-and-urinary-cd80-levels-in-children-with-idiopathic-nephrotic-syndrome
#4
Om P Mishra, Ravindra Kumar, Gopeshwar Narayan, Pradeep Srivastava, Abhishek Abhinay, Rajniti Prasad, Ankur Singh, Vineeta V Batra
BACKGROUND: The aims of this study were (1) to detect toll-like receptor (TLR)-3, TLR-4 and CD80 expression in peripheral blood mononuclear cells (PBMCs) and estimate urinary CD80 levels in children with idiopathic nephrotic syndrome and (2) to investigate the utility of these markers to differentiate between biopsy-proven minimal change disease (MCD) and focal segmental glomeruloscelerosis (FSGS). METHODS: The study included 70 patients with idiopathic nephrotic syndrome (NS), of whom 40 had steroid-sensitive NS (SSNS; 25 with active NS, 15 in remission) and 30 had steroid-resistant NS (SRNS) patients, and 23 healthy controls...
February 16, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28210782/toll-like-receptor-signaling-and-stages-of-addiction
#5
REVIEW
Fulton T Crews, T Jordan Walter, Leon G Coleman, Ryan P Vetreno
BACKGROUND: Athina Markou and her colleagues discovered persistent changes in adult behavior following adolescent exposure to ethanol or nicotine consistent with increased risk for developing addiction. Building on Dr. Markou's important work and that of others in the field, researchers at the Bowles Center for Alcohol Studies have found that persistent changes in behavior following adolescent stress or alcohol exposure may be linked to induction of immune signaling in brain. AIM: This study aims to illuminate the critical interrelationship of the innate immune system (e...
February 17, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28210435/role-of-thr399ile-and-asp299gly-polymorphisms-of-toll-like-receptor-4-gene-in-acute-dental-abscess
#6
Ebrahim Miri-Moghaddam, Narges Farhad-Mollashahi, Elnaz Baghaee, Ali Bazi, Yasaman Garme
BACKGROUND: Apical Periodontitis (AP) is an inflammatory disease that affects the tissues surrounding the root end of a tooth. The disease which is caused by endodontic infections presents in different clinical ways including development of an acute abscess. Recent studies have provided information suggesting role of a multitude of factors in pathogenesis of acute apical abscess (AAA). In this case-control study, our goal was to evaluate the frequency and potential role of two common polymorphisms of toll like receptor-4 (TLR-4) gene; Thr399Ile (1196 C>T) and Asp299Gly (+896 A>G), in 50 patients with AAA as cases and 50 patients with asymptomatic apical periodontitis (AAP) as controls...
February 2017: Journal of Clinical and Experimental Dentistry
https://www.readbyqxmd.com/read/28209713/mir-718-represses-pro-inflammatory-cytokine-production-through-targeting-pten
#7
Parisa Kalantari, Omid F Harandi, Sarika Agarwal, Florentina Rus, Evelyn A Kurt-Jones, Katherine A Fitzgerald, Daniel R Caffrey, Douglas T Golenbock
Bacterial sepsis involves a complex interaction between the host immune response and bacterial lipopolysaccharides (LPS). LPS binds Toll-like receptor (TLR) 4, which leads to the release of pro-inflammatory cytokines that are essential for a potent innate immune response against pathogens. The innate immune system is tightly regulated as excessive inflammation can lead to organ failure and death. MicroRNAs have recently emerged as important regulators of the innate immune system. Here, we determined the function of miR-718, which is conserved across mammals and overlaps with the 5 UTR of the Interleukin-1 Receptor-Associated Kinase (IRAK1) gene...
February 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28209121/evolution-of-toll-like-receptors-in-the-context-of-terrestrial-ungulates-and-cetaceans-diversification
#8
Edson Ishengoma, Morris Agaba
BACKGROUND: Toll-like receptors (TLRs) are the frontline actors in the innate immune response to various pathogens and are expected to be targets of natural selection in species adapted to habitats with contrasting pathogen burdens. The recent publication of genome sequences of giraffe and okapi together afforded the opportunity to examine the evolution of selected TLRs in broad range of terrestrial ungulates and cetaceans during their complex habitat diversification. Through direct sequence comparisons and standard evolutionary approaches, the extent of nucleotide and protein sequence diversity in seven Toll-like receptors (TLR2, TLR3, TLR4, TLR5, TLR7, TLR9 and TLR10) between giraffe and closely related species was determined...
February 16, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28208028/early-life-wildfire-smoke-exposure-is-associated-with-immune-dysregulation-and-lung-function-decrements-in-adolescence
#9
Carolyn Black, Joan E Gerriets, Justin H Fontaine, Richart W Harper, Nicholas J Kenyon, Fern Tablin, Edward S Schelegle, Lisa A Miller
RATIONALE: The long-term health effects of wildfire smoke exposure in pediatric populations are not known. OBJECTIVE: To determine if early life exposure to wildfire smoke can affect parameters of immunity and airways physiology that are detectable with maturity. METHODS: We studied a mixed gender cohort of rhesus macaque monkeys that were exposed as infants to ambient wood smoke from a series of Northern California wildfires in the summer of 2008...
February 16, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28207251/cross-linked-micellar-spherical-nucleic-acids-from-thermoresponsive-templates
#10
Resham J Banga, Brian Meckes, Suguna P Narayan, Anthony J Sprangers, SonBinh T Nguyen, Chad A Mirkin
A one-pot synthesis of micellar spherical nucleic acid (SNA) nanostructures using Pluronic F127 as a thermoresponsive template is reported. These novel constructs are synthesized in a chemically straightforward process that involves intercalation of the lipid tails of DNA amphiphiles (CpG motifs for TLR-9 stimulation) into the hydrophobic regions of Pluronic F127 micelles followed by chemical cross-linking and subsequent removal of non-crosslinked structures. The dense nucleic acid shell of the resulting cross-linked micellar SNA enhances their stability in physiological media and facilitates their rapid cellular internalization making them effective TLR-9 immunomodulatory agents...
February 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28204830/monoclonal-antibody-against-toll-like-receptor%C3%A2-4-attenuates-ventilator-induced-lung-injury-in-rats-by-inhibiting-myd88-and-nf-%C3%AE%C2%BAb-dependent-signaling
#11
Cuiyuan Huang, Linghui Pan, Fei Lin, Huijun Dai, Ruili Fu
The mechanisms through which mechanical ventilation causes non-infectious inflammatory diseases and lung injury are poorly understood. Animals models of this type of injury suggest that it involves signaling mediated by Toll‑like receptor (TLR)4 and 9. In this study, in order to gain further insight into the involvement of TLR4 in this type of injury, we performed in vivo and in vitro experiments to determine the mechanisms through which TLR4 triggers inflammation. We also examined whether the use of TLR4 monoclonal antibody (mAb) can alleviate this type of injury...
February 1, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28202909/leukocyte-tlr5-deficiency-inhibits-atherosclerosis-by-reduced-macrophage-recruitment-and-defective-t-cell-responsiveness
#12
Guilielmus H J M Ellenbroek, Gijs H M van Puijvelde, Adam A Anas, Martine Bot, Miriam Asbach, Arjan Schoneveld, Peter J van Santbrink, Amanda C Foks, Leo Timmers, Pieter A Doevendans, Gerard Pasterkamp, Imo E Hoefer, Tom van der Poll, Johan Kuiper, Saskia C A de Jager
Toll-like receptors (TLR) provide a critical link between innate and adaptive immunity, both important players in atherosclerosis. Since evidence for the role of TLR5 is lacking, we aimed to establish this in the immune axis of atherosclerosis. We assessed the effect of the TLR5-specific ligand Flagellin on macrophage maturation and T-cell polarisation. Next, we generated TLR5(-/-)LDLr(-/-) chimeras to study the effect of hematopoietic TLR5 deficiency on atherosclerosis formation. Flagellin stimulation did not influence wildtype or TLR5(-/-) macrophage maturation...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202625/gut-microbiota-promotes-obesity-associated-liver-cancer-through-pge2-mediated-suppression-of-antitumor-immunity
#13
Tze Mun Loo, Fumitaka Kamachi, Yoshihiro Watanabe, Shin Yoshimoto, Hiroaki Kanda, Yuriko Arai, Yaeko Nakajima-Takagi, Atsushi Iwama, Tomoaki Koga, Yukihiko Sugimoto, Takayuki Ozawa, Masaru Nakamura, Miho Kumagai, Koichi Watashi, Makoto M Taketo, Tomohiro Aoki, Shuh Narumiya, Masanobu Oshima, Makoto Arita, Eiji Hara, Naoko Ohtani
Obesity increases the risk of cancers, including hepatocellular carcinomas (HCCs). However, the precise molecular mechanisms through which obesity promotes HCC development are still unclear. Recent studies have shown that gut microbiota may influence liver diseases by transferring its metabolites and components. Here, we show that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment...
February 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28199901/cd44-deficiency-enhanced-streptococcus-equi-ssp-zooepidemicus-dissemination-and-inflammation-response-in-a-mouse-model
#14
Qiang Fu, Pingping Xiao, Yaosheng Chen, Zigong Wei, Xiaohong Liu
Streptococcus equi ssp. zooepidemicus (S. zooepidemicus) is responsible for peritonitis, septicemia, meningitis, arthritis and several other serious diseases in various species. Recent studies have demonstrated that CD44 is implicated in the process of host defense against pathogenic microorganisms. In the present study, the role of CD44 in the host response to S. zooepidemicus infection was investigated in a mouse model. Upon intraperitoneal infection with S. zooepidemicus, the expression of CD44 on the peritoneal exudate cells from wild-type (WT) mice was increased...
February 9, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28199836/bcr-and-endosomal-tlr-signals-synergize-to-increase-aid-expression-and-establish-central-b-cell-tolerance
#15
Masayuki Kuraoka, Pilar B Snowden, Takuya Nojima, Laurent Verkoczy, Barton F Haynes, Daisuke Kitamura, Garnett Kelsoe
Activation-induced cytidine deaminase (AID) is required to purge autoreactive immature and transitional-1 (immature/T1) B cells at the first tolerance checkpoint, but how AID selectively removes self-reactive B cells is unclear. We now show that B cell antigen receptor (BCR) and endosomal Toll-like receptor (TLR) signals synergize to elicit high levels of AID expression in immature/T1 B cells. This synergy is restricted to ligands for endocytic TLR and requires phospholipase-D activation, endosomal acidification, and MyD88...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28198500/molecular-characterization-expression-and-functional-analysis-of-chicken-traf6
#16
J Jin, J S Ran, C W Yang, X S Jiang, Y G Zhou, Z Q Feng, Y Wang, D Lan, P Ren, Y P Liu
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a crucial adaptor molecule of the interleukin-1 receptor/Toll-like receptor (IL-1/TLR) superfamily, which can trigger downstream signaling cascades involved in innate immunity. The function of TRAF6 has been clarified in mammals but is poorly understood in chicken. In our study, we investigated TRAF6 function in birds, particularly in chicken innate immune responses, by cloning and characterizing chicken TRAF6 (chTRAF6). The full-length coding sequence of chTRAF6 comprised 1638 bp and encoded a 545-amino acid protein, which shares high sequence similarity with TRAF6 of other species and consists of four structurally conserved domains...
February 8, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28198368/tlr4-signaling-induces-tlr3-up-regulation-in-alveolar-macrophages-during-acute-lung-injury
#17
Xibing Ding, Shuqing Jin, Yao Tong, Xi Jiang, Zhixia Chen, Shuya Mei, Liming Zhang, Timothy R Billiar, Quan Li
Acute lung injury is a life-threatening inflammatory response caused by severe infection. Toll-like receptors in alveolar macrophages (AMΦ) recognize the molecular constituents of pathogens and activate the host's innate immune responses. Numerous studies have documented the importance of TLR-TLR cross talk, but few studies have specifically addressed the relationship between TLR4 and TLR3. We explored a novel mechanism of TLR3 up-regulation that is induced by LPS-TLR4 signaling in a dose- and time-dependent manner in AMΦ from C57BL/6 mice, while the LPS-induced TLR3 expression was significantly reduced in TLR4(-/-) and Myd88(-/-) mice and following pretreatment with a NF-κB inhibitor...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193238/transient-ikk2-activation-in-astrocytes-initiates-selective-non-cell-autonomous-neurodegeneration
#18
Michael Lattke, Stephanie N Reichel, Alexander Magnutzki, Alireza Abaei, Volker Rasche, Paul Walther, Dinis P Calado, Boris Ferger, Thomas Wirth, Bernd Baumann
BACKGROUND: Neuroinflammation is associated with a wide range of neurodegenerative disorders, however the specific contribution to individual disease pathogenesis and selective neuronal cell death is not well understood. Inflammatory cerebellar ataxias are neurodegenerative diseases occurring in various autoimmune/inflammatory conditions, e.g. paraneoplastic syndromes. However, how inflammatory insults can cause selective cerebellar neurodegeneration in the context of these diseases remains open, and appropriate animal models are lacking...
February 13, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28192731/isotrifoliol-inhibits-pro-inflammatory-mediators-by-suppression-of-tlr-nf-%C3%AE%C2%BAb-and-tlr-mapk-signaling-in-lps-induced-raw264-7-cells
#19
Hua Li, Jeong-Hyun Yoon, Hyo-Jun Won, Hyeon-Seon Ji, Heong Joo Yuk, Ki Hun Park, Ho-Yong Park, Tae-Sook Jeong
Soybeans, produced by Glycine max (L.) Merr., contain high levels of isoflavones, such as genistein and daidzein. However, soy leaves contain more diverse and abundant flavonol glycosides and coumestans, as compared to the soybean. This study investigated the anti-inflammatory effects of the major coumestans present in soy leaf (coumestrol, isotrifoliol, and phaseol) in lipopolysaccharide (LPS)-induced RAW264.7 cells. Coumestans significantly reduced LPS-induced nitric oxide (NO), prostaglandin E2 (PGE2), and reactive oxygen species (ROS) production; isotrifoliol had the most potent anti-inflammatory activity...
February 10, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28192646/higher-expression-of-toll-like-receptors-3-7-8-and-9-in-pityriasis-rosea
#20
Mostafa Abou El-Ela, Mohamed El-Komy, Rania Abdel Hay, Rehab Hegazy, Amin Sharobim, Laila Rashed, Khalda Sayed Amr
Background: Pityriasis rosea (PR) is a common papulosquamous skin disease in which an infective agent may be implicated. Toll-like receptors (TLRs) play an important role in immune responses and in the pathophysiology of inflammatory skin diseases. Our aim was to determine the possible roles of TLRs 3, 7, 8, and 9 in the pathogenesis of PR. Materials and Methods: Twenty-four PR patients and 24 healthy individuals (as controls) were included in this case control study...
February 13, 2017: Journal of Pathology and Translational Medicine
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