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Tlr4, tlr2, toll like receptor,

Pei-Pei Xu, Qing-Feng Li, Yong-Mei Cui, Hai-Xia Lin
A series of paclitaxel analogs modified at C-3'-N and C-7 positions were synthesized from baccatin III and their structures were confirmed by (1)H-NMR, (13)C-NMR, HR-MS. Compound 7e exhibited potent ability to decrease TNFα (tumor necrosis factor α) in the LPS-activated RAW264.7 murine macrophage-like cell line. The preliminary data indicated that the anti-inflammatory effects may be related to MD-2 and Toll-like receptor 4 (TLR4), rather than Toll-like receptor 2 (TLR2).
October 18, 2016: Journal of Asian Natural Products Research
Raphaela Mayerhofer, Esther E Fröhlich, Florian Reichmann, Aitak Farzi, Nora Kogelnik, Eleonore Fröhlich, Wolfgang Sattler, Peter Holzer
Microbial metabolites are known to affect immune system, brain, and behavior via activation of pattern recognition receptors such as Toll-like receptor 4 (TLR4). Unlike the effect of the TLR4 agonist lipopolysaccharide (LPS), the role of other TLR agonists in immune-brain communication is insufficiently understood. We therefore hypothesized that the TLR2 agonist lipoteichoic acid (LTA) causes immune activation in the periphery and brain, stimulates the hypothalamic-pituitary-adrenal (HPA) axis and has an adverse effect on blood-brain barrier (BBB) and emotional behavior...
October 14, 2016: Brain, Behavior, and Immunity
Bruno Sangiorgi, Rodrigo Alexandre Panepucci
In the last decade, the immunomodulatory properties of mesenchymal stromal cells (MSCs) have attracted a lot of attention, due to their potential applicability in the treatment of graft-versus-host disease (GVHD), a condition frequently associated with opportunistic infections. The present review addresses how Pathogen-Associated Molecular Patterns (PAMPS) modulate the immunosuppressive phenotype of human MSCs by signaling through Toll-like receptors (TLRs). Overall, we observed that regardless of the source tissue, human MSCs express TLR2, TLR3, TLR4, and TLR9...
2016: Stem Cells International
Juneo F Silva, Natália M Ocarino, Rogéria Serakides
The gene and/or protein expression of proteases and immunological, angiogenic, hormonal and apoptotic mediators was evaluated in rat placenta before and during intrauterine trophoblast migration. The depth of interstitial and endovascular intrauterine trophoblast invasion and the immunohistochemical expression of vascular endothelial growth factor (VEGF), fetal liver kinase 1 (Flk1), interferon (IFN)-γ, migration inhibitory factor (MIF), and inducible nitric oxide synthase (iNOS; also known as nitric oxide synthase (NOS) 2) were evaluated...
October 14, 2016: Reproduction, Fertility, and Development
Qi Zhong, Kai Zhou, Qiao-Li Liang, Sen Lin, Yan-Chun Wang, Xiao-Yi Xiong, Zhao-You Meng, Ting Zhao, Wen-Yao Zhu, Yuan-Rui Yang, Mao-Fan Liao, Qiu-Wen Gong, Liang Liu, Ao Xiong, Junwei Hao, Jian Wang, Qing-Wu Yang
BACKGROUND: Neuroinflammation plays a key role in intracerebral hemorrhage (ICH)-induced secondary brain injury, but the specific roles of peripheral inflammatory cells such as macrophages and lymphocytes remain unknown. The purpose of this study was to explore the roles of macrophages, T lymphocytes, and the cytokines they secrete as potential targets for treating secondary brain injury after ICH. METHODS AND RESULTS: Our results showed that peripheral macrophages and T lymphocytes successively infiltrated the brain, with macrophage counts peaking 1 day after ICH and T-lymphocyte counts peaking after 4 days...
October 11, 2016: Journal of the American Heart Association
Tamara V Smelaya, Olesya B Belopolskaya, Svetlana V Smirnova, Artem N Kuzovlev, Viktor V Moroz, Arkadiy M Golubev, Noel A Pabalan, Lyubov E Salnikova
The role of host genetic variation in pneumonia development and outcome is poorly understood. We studied common polymorphisms in the genes of proinflammatory cytokines (IL6 rs1800795, IL8 rs4073, IL1B rs16944), anti-inflammatory cytokines (IL10 rs1800896, IL4 rs2243250, IL13 rs20541) and toll-like receptors (TLR2 rs5743708 and rs4696480, TLR4 rs4986791, TLR9 rs352139, rs5743836 and rs187084) in patients with community-acquired pneumonia (CAP) (390 cases, 203 controls) and nosocomial pneumonia (355 cases, 216 controls)...
October 11, 2016: Scientific Reports
Soon-Youn Choi, Hye-Myung Ryu, Ji-Young Choi, Jang-Hee Cho, Chan-Duck Kim, Yong-Lim Kim, Sun-Hee Park
PURPOSE: High glucose stimulates peritoneal inflammation and extracellular matrix accumulation in human peritoneal mesothelial cells (HPMCs). However, the roles of Toll-like receptor 4 (TLR4) and TLR2 in high-glucose-induced inflammation and fibrosis in peritoneal dialysis (PD) remain unclear. This study aimed to evaluate the effect of high glucose on TLR2 and TLR4 expression in HPMCs and to assess their impact on peritoneal inflammatory and fibrosis markers. METHODS: Using cultured HPMCs, TLRs expression by high-glucose (50 mM) stimulation was assessed by quantitative real-time PCR...
October 8, 2016: International Urology and Nephrology
Diana M Giraldo, Juan C Hernandez, Silvio Urcuqui-Inchima
Neutrophils are key effector cells of the innate immune system and are involved in the host defense against invading pathogens such as viruses. Recently, it was reported that HIV-1-neutrophil interaction triggers neutrophil activation and promotes expression of Toll-like receptors (TLRs). Here, we assessed the role of single-stranded RNA40 (ssRNA40) derived from HIV-1 in neutrophil activation. We observed functional activation of neutrophils in response to HIV-1-derived ssRNA40 based on the expression of TLR7/8, RIG-I, and MDA5, induction of cytokines (IL-6 and TNF-α), and the production of reactive oxygen species (ROS)...
October 7, 2016: Immunologic Research
Alice Halliday, Paul A Bates, Michael L Chance, Mark J Taylor
BACKGROUND: Leishmaniasis is a neglected tropical disease affecting millions of individuals worldwide. Despite several studies reporting involvement of the innate immune receptor Toll-like receptor 2 (TLR2) in the recognition of surface glycolipids from Leishmania parasites in vitro, the role of TLR2 and its co-receptors during cutaneous leishmaniasis infection in vivo is unknown. METHODS: To explore the role of TLR2 and its co-receptors in cutaneous leishmaniasis, mice deficient in either TLR2, 4, 1 or 6, or wild-type (WT) controls, were infected with either Leishmania major promastigotes, L...
October 6, 2016: Parasites & Vectors
Tobias Hilbert, Kathrin Dornbusch, Georg Baumgarten, Andreas Hoeft, Stilla Frede, Sven Klaschik
Increased pulmonary vascular resistance is a critical complication in sepsis. Toll-like receptor (TLR) as well as angiopoietin (ANG) signaling both contribute to the emergence of pulmonary arterial hypertension. We hypothesized that TLR stimulation by bacterial ligands directly affects expression and secretion of ligands and receptors of the angiopoietin/TIE axis. Microvascular endothelial (HPMEC) and smooth muscle cells (SMC) of pulmonary origin were incubated with thrombin and with ligands for TLR2, -4, -5, and -9...
October 6, 2016: Clinical and Experimental Pharmacology & Physiology
Kambis Sadeghi, Lukas Wisgrill, Isabelle Wessely, Susanne C Diesner, Simone Schüller, Celia Dürr, Armando Heinle, Monika Sachet, Arnold Pollak, Elisabeth Förster-Waldl, Andreas Spittler
Toll-like receptors (TLR) are crucial sensors of microbial agents such as bacterial or viral compounds. These receptors constitute key players in the induction of inflammation, e.g. in septic or chronic inflammatory diseases. Colony-stimulating factors (CSFs) such as granulocyte-macrophage-CSF (GM-CSF) or granulocyte-CSF (G-CSF) have been extensively investigated in their capacity to promote myelopoiesis in febrile neutropenia or to overcome immunosuppression in patients suffering from sepsis-associated neutropenia or from monocytic immunoincompetence...
2016: PloS One
Sara Montserrat-Sangrà, Lorena Alborch, Laura Ordeix, Laia Solano-Gallego
Innate immunity, in particular, the role of toll-like receptors (TLRs), has not been extensively studied in canine L. infantum infection. The main aim of this study was to determine the transcription of TLR2 and TLR4 in the blood of dogs with natural clinical leishmaniosis at the time of diagnosis and during treatment follow-up and subsequently correlate these findings with clinical, serological and parasitological data. Forty-six Leishmania-seropositive sick dogs with a high antibody level at the time of diagnosis were studied and compared with 34 healthy seronegative dogs...
September 15, 2016: Veterinary Parasitology
Ana T G Guerrero, Larissa G Pinto, Fernando Q Cunha, Sérgio H Ferreira, Jose C Alves-Filho, Waldiceu A Verri, Thiago M Cunha
BACKGROUND: Toll-like receptors (TLRs) including TLR4 and their signal pathways contribute to the pathogenesis of arthritis. Herein, we evaluated the mechanisms underlying the hyperalgesic response caused by TLR4 activation in the tibio-tarsal joint in mice. METHODS: Joint inflammatory hyperalgesia was induced by intra-articular (ia) injection of LPS (lipopolysaccharide- TLR4 agonist) in C57BL/6, TLR4, TLR2, MyD88, TRIF, TNFR1/2 and IL-1R1 knockout ((-/-)) mice...
August 24, 2016: Pharmacological Reports: PR
Sanja Stopinšek, Alojz Ihan, Barbara Salobir, Marjeta Terčelj, Saša Simčič
BACKGROUND: Composition of organic dust is very complex, involving particles of microbial, animal and plant origin. Several environmental exposure studies associate microbial cell wall agents in organic dust with various respiratory symptoms and diseases. The aim of the present study was to investigate the in vitro effects of the co-exposure of fungal cell wall agents (FCWAs) and bacterial lipopolysaccharide (LPS) on inflammatory immune responses of peripheral blood mononuclear cells (PBMCs) from patients with pulmonary sarcoidosis...
2016: Journal of Occupational Medicine and Toxicology
Xu Zhang, Na Li, Yan Meng, Renjing Zhang, Jinjun Bian, Ying Yao, Jinbao Li, Xiaoming Deng
BACKGROUND As a serious clinical problem, severe burn injury disturbs the immune system, resulting in progressive suppression of immune response. TLRs are associated with immune system activation, but the effect of TLRs levels on circulating cDCs of severe burn injury patients has not been fully assessed. MATERIAL AND METHODS Ten patients with total body surface area (TBSA) burned >90% admitted to our institution were enrolled in this study. We analyzed TLR2, TLR4, and TLR9 expression on the circulating cDCs by using multicolor flow cytometric analysis in patients at 14 days to 28 days after burn injury according to mortality, and We also assessed Demographics, clinical outcomes, organ function, and inflammatory and acute-phase responses...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Jonathan Laiño, Julio Villena, Paulraj Kanmani, Haruki Kitazawa
Researchers have demonstrated that lactic acid bacteria (LAB) with immunomodulatory capabilities (immunobiotics) exert their beneficial effects through several molecules, including cell wall, peptidoglycan, and exopolysaccharides (EPS), that are able to interact with specific host cell receptors. EPS from LAB show a wide heterogeneity in its composition, meaning that biological properties depend on the strain and. therefore, only a part of the mechanism of action has been elucidated for these molecules. In this review, we summarize the current knowledge of the health-promoting actions of EPS from LAB with special focus on their immunoregulatory actions...
August 15, 2016: Microorganisms
Naga Suresh Adapala, Ryosuke Yamaguchi, Matthew Phipps, Olumide Aruwajoye, Harry K W Kim
In children with Legg-Calvé-Perthes disease, loss of blood supply to the femoral head results in ischemic osteonecrosis. Generally, macrophages play important roles in the inflammatory response to tissue necrosis, but their role in ischemic osteonecrosis of the femoral head (ONFH) is not known. The purpose of this study was to determine the macrophage-inflammatory responses after ONFH and the receptor mechanisms involved in sensing the necrotic bone, using a piglet model of Legg-Calvé-Perthes disease. Induction of ONFH resulted in increased numbers of CD14(+) macrophages (4...
September 17, 2016: American Journal of Pathology
Perla Villani Borges, Katelim Hottz Moret, Raghavendra Nulgumnalli Manjunathaiah, Thadeu Estevam Maramaldo Costa, Ana Paula Monteiro, Alan Brito Carneiro, Patrícia Pacheco, Jairo Ramos Temerozo, Dumith Chequer Bou-Habib, Maria das Graças Henriques, Carmen Penido
Activation of toll-like receptors (TLRs) by pathogen-associated molecular patterns (PAMPs) triggers an innate immune response, via cytokine production and inflammasome activation. Herein, we have investigated the modulatory effect of the natural limonoid gedunin on TLR activation in vitro and in vivo. Intraperitoneal (i.p.) pre- and post-treatments of C57BL/6 mouse with gedunin impaired the influx of mononuclear cells, eosinophils and neutrophils, as well as the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and nitric oxide (NO), triggered by lipopolysaccharide (LPS) in mouse pleura...
September 15, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Yijie Guo, Cuiping Ding, Bo Zhang, Jun Xu, Meng Xun, Jiru Xu
BACKGROUND: Bovine leptospirosis is a widespread zoonotic disease, leading to serious economic losses in animal production and causing potential hazards to human health. Leptospiral lipopolysaccharide (L-LPS) plays an important role in leptospirosis pathogenicity. OBJECTIVES: With respect to L-LPS endotoxin-like activity, we examined bovine immune response to L-LPS and the inhibitory ability of bovine myeloid antimicrobial peptide-28 (BMAP-28) against L-LPS-induced immune activation in bovine cells...
June 2016: Jundishapur Journal of Microbiology
Valentina Salvi, Xenia Vaira, Veronica Gianello, William Vermi, Mattia Bugatti, Silvano Sozzani, Daniela Bosisio
PGE2 is a lipid mediator abundantly produced in inflamed tissues that exerts relevant immunoregulatory functions. Dendritic cells (DCs) are key players in the onset and shaping of the inflammatory and immune responses and, as such, are well known PGE2 targets. By contrast, the precise role of human DCs in the production of PGE2 is poorly characterized. Here, we asked whether different ligands of Toll-like receptors (TLRs), a relevant family of pathogen-sensing receptors, could induce PGE2 in human DCs. The only active ligands were LPS (TLR4 ligand) and R848 (TLR7-8 ligand) although all TLRs, but TLR9, were expressed and functional...
2016: Mediators of Inflammation
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