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https://www.readbyqxmd.com/read/28432147/cutting-edge-a-dual-tlr2-and-tlr7-ligand-induces-highly-potent-humoral-and-cell-mediated-immune-responses
#1
Alice Gutjahr, Laura Papagno, Francesco Nicoli, Alain Lamoureux, Fabienne Vernejoul, Thierry Lioux, Emma Gostick, David A Price, Gérard Tiraby, Eric Perouzel, Victor Appay, Bernard Verrier, Stéphane Paul
TLR agonists are currently being developed and tested as adjuvants in various formulations to optimize the immunogenicity and efficacy of vaccines. The aim of this study was to evaluate the immunostimulatory properties of a novel compound incorporating covalently linked moieties designed to stimulate both TLR2 and TLR7. This dual TLR2/TLR7 agonist induced the maturation of dendritic cells and primed substantial populations of cytolytic and highly polyfunctional effector CD8(+) T cells in vitro, and safely potentiated the immunogenic properties of a nanoparticulate Ag in vivo, eliciting humoral responses with a balanced TH1/TH2 profile in mice...
April 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28432060/toll-like-receptor-2-tlr2-dominance-over-tlr4-in-stressful-conditions-for-its-detrimental-role-in-the-heart
#2
Ashim K Bagchi, Gauri Akolkar, Soma Mandal, Prathapan Ayyappan, Xi Yang, Pawan K Singal
It has been suggested that toll-like receptor 4 (TLR4) promotes interleukin-10 (IL-10)-mediated cardiac cell survival while another receptor, TLR2, from the same family is detrimental. Here we examined the interactive role of these two innate signaling molecules under stressful conditions including interleukin-10 knockout (IL-10(-/-)) mice, global ischemia/reperfusion (I/R) injury in rat hearts and in-vitro shRNA experimental models in presence or absence of IL-10 (10ng/ml). Circulating and myocardial levels of tumor necrosis factor-α (TNF-α) as well as apoptosis and fibrosis were higher in IL-10(-/-) mice...
April 21, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28432035/expression-of-pattern-recognition-receptors-and-activation-of-the-non-canonical-inflammasome-pathway-in-brain-pericytes
#3
Ádám Nyúl-Tóth, Mihály Kozma, Péter Nagyőszi, Krisztina Nagy, Csilla Fazakas, János Haskó, Kinga Molnár, Attila E Farkas, Attila G Végh, György Váró, Péter Galajda, Imola Wilhelm, István A Krizbai
Cerebral pericytes are mural cells embedded in the basement membrane of capillaries. Increasing evidence suggests that they play important role in controlling neurovascular functions, i.e. cerebral blood flow, angiogenesis and permeability of the blood-brain barrier. These cells can also influence neuroinflammation which is highly regulated by the innate immune system. Therefore, we systematically tested the pattern recognition receptor expression of brain pericytes. We detected expression of NOD1, NOD2, NLRC5, NLRP1-3, NLRP5, NLRP9, NLRP10 and NLRX mRNA in non-treated cells...
April 18, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28428684/innate-immunity-of-adipose-tissue-in-rodent-models-of-local-and-systemic-staphylococcus-aureus-infection
#4
Andreas Schmid, Thomas Karrasch, Miriam Thomalla, Jutta Schlegel, Bernd Salzberger, Andreas Schäffler, Frank Hanses
Background. The role of adipose tissue in systemic inflammation during bacterial infection is unclear. Effects of Staphylococcus aureus infection on adipocytes in rodent models of experimental endocarditis and peritonitis, the impact of S. aureus infection on gene expression in epididymal and subcutaneous adipose tissue, and effects of S. aureus infection on the toll-like receptor-2- (TLR2-) cathelicidin pathway in vivo and in vitro were investigated. Material and methods. The rat model of catheter-induced S...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28428204/flow-perturbation-mediates-neutrophil-recruitment-and-potentiates-endothelial-injury-via-tlr2-in-mice-implications-for-superficial-erosion
#5
Grégory Franck, Thomas Mawson, Grasiele Sausen, Manuel Salinas, Gustavo Santos Masson, Andrew P Cole, Marina Beltrami Moreira, Yiannis Chatzizisis, Thibaut Quillard, Yevgenia Tesmenitsky, Eugenia Shvartz, Galina K Sukhova, Filip K Swirski, Matthias Nahrendorf, Elena Aikawa, Kevin Croce, Peter Libby
Rationale: Superficial erosion currently causes up to a third of acute coronary syndromes (ACS), yet we lack understanding of its mechanisms. Thrombi due to superficial intimal erosion characteristically complicate matrix-rich atheromata in regions of flow perturbation. Objective: This study tested in vivo the involvement of disturbed flow, and of neutrophils, hyaluronan, and TLR2 ligation in superficial intimal injury, a process implicated in superficial erosion. Methods and Results: In mouse carotid arteries with established intimal lesions tailored to resemble the substrate of human eroded plaques, acute flow perturbation promoted downstream endothelial cell (EC) activation, neutrophil accumulation, EC death and desquamation, and mural thrombosis...
April 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/28427896/toll-like-receptor-2-an-important-immunomodulatory-molecule-during-helicobacter-pylori-infection
#6
REVIEW
Maryam Nemati, Tiziana Larussa, Hossein Khorramdelazad, Merat Mahmoodi, Abdollah Jafarzadeh
Toll like receptors (TLRs) are an essential subset of pathogen recognition receptors (PRRs) which identify the microbial components and contribute in the regulation of innate and adaptive immune responses against the infectious agents. The TLRs, especially TLR2, TLR4, TLR5 and TLR9, participate in the induction of immune response against H. pylori. TLR2 is expressed on a number of immune and non-immune cells and recognizes a vast broad of microbial components due to its potential to form heterodimers with other TLRs, including TLR1, TLR6 and TLR10...
April 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28427050/expression-of-high-mobility-group-protein-b1-in-cardiac-tissue-of-elderly-patients-with-coronary-artery-disease-with-or-without-inflammatory-rheumatic-disease
#7
Mei Bruton, Ivana Hollan, Julie Xiao, Eva Lindroos, Knut Mikkelsen, Stein E Rynning, Kjell Saatvedt, Sven M Almdahl, Helena E Harris, Ingrid E Lundberg, Cecilia Wick
BACKGROUND: It is known from clinical practice and observational studies that elderly patients with a diagnosis of inflammatory rheumatic diseases (IRD) bear a significantly increased risk for cardiovascular diseases such as coronary artery disease (CAD) and heart failure. The molecular mechanism, however, is still not known. Recently, high mobility group protein B1 (HMGB1), a ubiquitous, highly conserved single polypeptide expressed in all mammal eukaryotic cells, has been identified to mediate myocardial dysfunction in vitro once released from the nuclei of cardiomyocytes...
April 21, 2017: Gerontology
https://www.readbyqxmd.com/read/28425217/the-release-of-pro-inflammatory-cytokines-is-mediated-via-map-kinases-rather-than-inflammasome-signaling-pathway-in-keratinocytes
#8
Thomas Ondet, Béatrice Muscatelli-Groux, Cédric Coulouarn, Sacha Robert, Thomas Gicquel, Aude Bodin, Vincent Lagente, Jean-Alexis Grimaud
Toll like receptors (TLRs) are expressed in the skin and airway epithelial tissues, which are the most important sites of host-pathogen interactions. TLRs recognize the three-dimensional structure of pathogen associated molecules and are thus useful markers of the innate immune response. Here, we investigated the role of lipopolysaccharides (LPS) and monosodium urate (MSU) crystals in the activation of the TLR and Nod Like Receptors (NLR) pathways in human keratinocytes. Analysis of the inflammasome compounds revealed that NLRP3 and TLR4, both of which are components of inflammasome complexes involved in the activation of IL-1β, were not expressed in keratinocytes...
April 20, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28424593/phospholipase-a2-of-peroxiredoxin-6-plays-a-critical-role-in-cerebral-ischemia-reperfusion-inflammatory-injury
#9
Yu Shanshan, Jiang Beibei, Tan Li, Gao Minna, Lei Shipeng, Peng Li, Zhao Yong
Microglia-mediated inflammation is an important step in the progression of cerebral ischemia/reperfusion injury and the associated production of receptors of immunomoudulation, including Toll-like receptors (TLRs). Peroxiredoxin 6 (Prdx6) has been demonstrated as the endogenous antioxidant protein for its peroxidase properties. However, the role of the independent phospholipase A2 (iPLA2) activity of Prdx6 in stroke has not been well studied. In this study, we evaluated whether blocking the calcium-iPLA2 activity of Prdx6 using siRNA and inhibitors (1-hexadecyl-3-(trifluoroethgl)-sn-glycerol-2 phosphomethanol, MJ33) would have a critical effect on inflammatory brain damage...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28423002/human-sr-bii-mediates-saa-uptake-and-contributes-to-saa-pro-inflammatory-signaling-in-vitro-and-in-vivo
#10
Irina N Baranova, Ana C P Souza, Alexander V Bocharov, Tatyana G Vishnyakova, Xuzhen Hu, Boris L Vaisman, Marcelo J Amar, Zhigang Chen, Alan T Remaley, Amy P Patterson, Peter S T Yuen, Robert A Star, Thomas L Eggerman
Serum amyloid A (SAA) is an acute phase protein with cytokine-like and chemotactic properties, that is markedly up-regulated during various inflammatory conditions. Several receptors, including FPRL-1, TLR2, TLR4, RAGE, class B scavenger receptors, SR-BI and CD36, have been identified as SAA receptors. This study provides new evidence that SR-BII, splice variant of SR-BI, could function as an SAA receptor mediating its uptake and pro-inflammatory signaling. The uptake of Alexa Fluor488 SAA was markedly (~3 fold) increased in hSR-BII-expressing HeLa cells when compared with mock-transfected cells...
2017: PloS One
https://www.readbyqxmd.com/read/28421347/tu-100-exerts-a-protective-effect-against-bacterial-translocation-by-maintaining-the-tight-junction
#11
Chie Takasu, Wubetu Gizachew Yismaw, Nobuhiro Kurita, Kozo Yoshikawa, Hideya Kashihara, Toru Kono, Mitsuo Shimada
PURPOSE: We previously reported that TU-100 suppresses irinotecan hydrochloride (CPT-11)-induced inflammatory cytokines and apoptosis. However, the mechanism underlying this effect has not been fully elucidated. The aim of this study was to further clarify the mechanism of CPT-11-induced bacterial translocation (BT) and the effect of TU-100 on BT. METHODS: Cell cytotoxicity was assessed in vitro by a WST-8 assay. For the in vivo experiments, rats were randomly divided into 3 groups: the control group, the CPT-11 group (250 mg/kg i...
April 18, 2017: Surgery Today
https://www.readbyqxmd.com/read/28419983/pam3csk4-induces-mmp-9-expression-in-human-monocytic-thp-1-cells
#12
Fatema Al-Rashed, Shihab Kochumon, Safa Usmani, Sardar Sindhu, Rasheed Ahmad
BACKGROUND: Matrix metalloproteinase (MMP)-9 is known to degrade the extracellular matrix and increased MMP-9 levels are related with the pathogenesis of many inflammatory conditions including obesity. Pam3CSK4 is a synthetic triacylated lipopeptide (LP) which is a potent activator of immune cells and induces cytokine production. However, it is unclear whether Pam3CSK4 is able to induce MMP-9 expression in monocytic cells. We, therefore, determined MMP-9 production by Pam3CSK4-treated THP-1 cells and also investigated the signal transduction pathway(s) involved...
April 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28419838/peptidoglycan-accelerates-granulopoiesis-through-a-tlr2-and-myd88-dependent-pathway
#13
Masaya Takehara, Soshi Seike, Teruhisa Takagishi, Keiko Kobayashi, Masahiro Nagahama
Granulopoiesis is accelerated during Gram-negative bacterial infection through activation of toll-like receptor 4 (TLR4). In this study, we tested whether activation of TLR2 promotes granulopoiesis by using the well-known TLR2 agonist, peptidoglycan (PGN). Neutrophils in bone marrow and spleen, and plasma granulocyte colony-stimulating factor (G-CSF) were increased in mice that had received intraperitoneal PGN administration. Incorporation of BrdU into bone marrow neutrophils increased, demonstrating that PGN accelerated granulopoiesis...
April 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28419472/hepatic-expression-of-oncogenes-bmi1-and-dkk1-is-up-regulated-in-hepatitis-b-virus-surface-antigen-transgenic-mice-and-can-be-induced-by-treatment-with-hbv-particles-or-lipopolysaccharides-in-vitro
#14
Rui Zhang, Catherine I Real, Chao Liu, Hideo A Baba, Guido Gerken, Mengji Lu, Ruth Broering
Previous studies have shown that hepatocellular carcinoma (HCC) develops more frequently in hepatitis B virus surface antigen (HBsAg)-transgenic mice (Alb/HBs) than in wild-type (WT) mice. However, the mechanism of this HCC model has not been well documented. Toll-like receptor 4 (Tlr4) signaling probably links innate immunity and HCC progression. The current study was designed to investigate the role of innate immunity in hepatocarcinogenesis in Alb/HBs mice. Immunohistochemical analysis of liver specimens from Alb/HBs mice (16 per group) showed that the oncogenes Bmi1 (16/16, 100%) and Dkk1 (13/16, 81...
April 17, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28418857/multi-factorial-modulation-of-colorectal-carcinoma-cells-motility-partial-coordination-by-the-tetraspanin-co-029-tspan8
#15
Yingying Zhu, Naouel Ailane, Monica Sala-Valdés, Farhad Haghighi-Rad, Martine Billard, Viet Nguyen, Raphael Saffroy, Antoinette Lemoine, Eric Rubinstein, Claude Boucheix, Céline Greco
Colorectal carcinoma cells Isreco1 display an ability to migrate controlled by a complex set of signals issued from the membrane. By comparing cells infected by mycoplasmas and mycoplasmas free cells, we have established that basal 2D migration is dependent on a double signal mediated by the collagen receptors integrins alpha1/2 and the Toll-Like receptor TLR2. The signal issued from mycoplasmas can be replaced by a TLR2 ligand and the functional effect is neutralized by silencing of MyD88. Following previous observation that downregulation of E-cadherin/p120 catenin increases cell motility, we now report that EGFR or CD44 inhibition have a similar effect on cell motility that is restricted to tetraspanin Co-029/tspan8 transduced IsrecoI cells (Is1-Co029)...
April 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418096/expression-of-toll-like-receptors-in-t-lymphocytes-stimulated-with-n-3-oxododecanoyl-l-homoserine-lactone-from-pseudomonas-aeruginosa
#16
Lei Bao, Jialin Yu, Haiying Zhong, Daochao Huang, Qi Lu
The establishment of chronic Pseudomonas aeruginosa infections is correlated with the disturbance of the host immune system. The P. aeruginosa quorum-sensing molecule N-3-(oxododecanoyl)-L-homoserine lactone (3-O-C12-HSL) has the potential to modulate the host immune system. The immune system recognizes pathogens via toll-like receptors (TLRs). We found that 3-O-C12-HSL induced TLR changes in monocytes. However, the role of T cells in P. aeruginosa infection has not been delineated. In order to understand this activity, we examined whether 3-O-C12-HSL has an effect on the immune function and the expression of TLRs in T lymphocytes...
April 18, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28418004/host-determinants-of-expression-of-the-helicobacter-pylori-baba-adhesin
#17
Mary E Kable, Lori M Hansen, Cathy M Styer, Samuel L Deck, Olena Rakhimova, Anna Shevtsova, Kathryn A Eaton, Miriam E Martin, Pär Gideonsson, Thomas Borén, Jay V Solnick
Expression of the Helicobacter pylori blood group antigen binding adhesin A (BabA) is more common in strains isolated from patients with peptic ulcer disease or gastric cancer, rather than asymptomatic colonization. Here we used mouse models to examine host determinants that affect H. pylori BabA expression. BabA expression was lost by phase variation as frequently in WT mice as in RAG2-/- mice that do not have functional B or T cells, and in MyD88-/-, TLR2-/- and TLR4-/- mice that are defective in toll like receptor signaling...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28418003/toll-like-receptor-polymorphisms-compromise-the-inflammatory-response-against-bacterial-antigen-translocation-in-cirrhosis
#18
Paula Piñero, Oriol Juanola, Esther Caparrós, Pedro Zapater, Paula Giménez, José M González-Navajas, José Such, Rubén Francés
Bacterial translocation is associated with clinically relevant complications in cirrhosis. We evaluated the effect of toll-like receptor polymorphisms in the soluble response against these episodes. Consecutive patients with cirrhosis and ascitic fluid were distributed by TLR2 rs4696480, TLR4 rs4986790, and TLR9 rs187084 single-nucleotide polymorphisms. Lipoteichoic acid, lipopolyssaccharide, bacterial-DNA, pro-inflammatory cytokines and nitric oxide levels were quantified in serum samples. In vitro response against specific ligands in variant TLR genotypes was evaluated...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28415707/luteolin-reduces-inflammation-in-staphylococcus-aureus-induced-mastitis-by-inhibiting-nf-kb-activation-and-mmps-expression
#19
Ying-Fang Guo, Nian-Nian Xu, Weijing Sun, Yifan Zhao, Cheng-Ye Li, Meng-Yao Guo
Mastitis is a serious and prevalent disease caused by infection by pathogens such as Staphylococcus aureus. We evaluated the anti-inflammatory effects and mechanism of luteolin, a natural flavonoid with a wide range of pharmacological activities, in a mouse model of S. aureus mastitis. We also treated cultured mouse mammary epithelial cells (mMECs) with S. aureus and luteolin. Histopathological changes were examined by H&E staining and the levels of inflammatory cytokine proteins were analyzed using ELISAs...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415700/circulating-tumor-cells-promote-the-metastatic-colonization-of-disseminated-carcinoma-cells-by-inducing-systemic-inflammation
#20
Yong-Chao Li, Jiu-Ming Zou, Chao Luo, Yu Shu, Jing Luo, Jian Qin, Yu Wang, Dong Li, Shan-Shan Wang, Gang Chi, Fang Guo, Gui-Mei Zhang, Zuo-Hua Feng
Circulating tumor cells (CTCs) have been studied well in the prognosis for malignant diseases as liquid biopsy, but their contribution to tumor metastasis is not clearly defined. Here we report that CTCs could promote the metastatic colonization of disseminated carcinoma cells by inducing systemic inflammation and neutrophil recruitment to pre-metastatic organs. Depletion of neutrophils in vivo could effectively abrogate the promoting effect of CTCs on tumor cell metastasis. In the presence of CTCs, the pro-tumor function of neutrophils was augmented, whereas the antitumor function of neutrophils was suppressed...
March 10, 2017: Oncotarget
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