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https://www.readbyqxmd.com/read/27934954/strap-acts-as-a-scaffolding-protein-in-controlling-the-tlr2-4-signaling-pathway
#1
Hyunbin D Huh, Eun A Ra, Taeyun A Lee, Sujin Kang, Areum Park, Eunhye Lee, Junhee L Choi, Eunji Jang, Ji Eun Lee, Sungwook Lee, Boyoun Park
The WD40-repeat protein serine/threonine kinase receptor-associated protein (STRAP) is involved in the regulation of several biological processes, including cell proliferation and apoptosis, in response to various stresses. Here, we show that STRAP is a new scaffold protein that functions in Toll-like receptor (TLR)-mediated immune responses. STRAP specifically binds transforming growth factor β-activated kinase 1 (TAK1) and IκB kinase alpha (IKKα) along with nuclear factor-κB (NF-κB) subunit p65, leading to enhanced association between TAK1, IKKα, and p65, and subsequent facilitation of p65 phosphorylation and nuclear translocation...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27934908/trem-2-promotes-acquired-cholesteatoma-induced-bone-destruction-by-modulating-tlr4-signaling-pathway-and-osteoclasts-activation
#2
Huaili Jiang, Yu Si, Zhuohao Li, Xi Huang, Suijun Chen, Yiqing Zheng, Guo Xu, Ximing Chen, Yubin Chen, Yi Liu, Hao Xiong, Qiuhong Huang, Maojin Liang, Zhigang Zhang
Triggering receptor expressed on myeloid cells (TREM) has been broadly studied in inflammatory disease. However, the expression and function of TREM-2 remain undiscovered in acquired cholesteatoma. The expression of TREM-2 was significantly higher in human acquired cholesteatoma than in normal skin from the external auditory canal, and its expression level was positively correlated with the severity of bone destruction. Furthermore, TREM-2 was mainly expressed on dendritic cells (DCs). In human acquired cholesteatoma, the expression of proinflammatory cytokines (IL-1β, TNF-α and IL-6) and matrix metalloproteinases (MMP-2, MMP-8 and MMP-9) were up-regulated, and their expression levels were positively correlated with TREM-2 expression...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27932984/curcumin-suppressed-activation-of-dendritic-cells-via-jak-stat-socs-signal-in-mice-with-experimental-colitis
#3
Hai-Mei Zhao, Rong Xu, Xiao-Ying Huang, Shao-Min Cheng, Min-Fang Huang, Hai-Yang Yue, Xin Wang, Yong Zou, Ai-Ping Lu, Duan-Yong Liu
Dendritic cells (DCs) play a pivotal role as initiators in the pathogenesis of inflammatory bowel disease and are regulated by the JAK/STAT/SOCS signaling pathway. As a potent anti-inflammatory compound, curcumin represents a viable treatment alternative or adjunctive therapy in the management of chronic inflammatory bowel disease (IBD). The mechanism of curcumin treated IBD on DCs is not completely understood. In the present study, we explored the mechanism of curcumin treated experimental colitis by observing activation of DCs via JAK/STAT/SOCS signaling pathway in colitis mice...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27932517/allergin-1-inhibits-tlr2-mediated-mast-cell-activation-and-suppresses-dermatitis
#4
Satoshi Tsurusaki, Satoko Tahara-Hanaoka, Shohei Shibagaki, Shota Miyake, Masamichi Imai, Shiro Shibayama, Masato Kubo, Akira Shibuya
TLR2 recognizes cell wall components of Staphylococcus aureus, which colonizes >90% of atopic eczematous skin lesions. The regulatory mechanisms of TLR2 signaling in the skin remain unclear. Allergin-1, an inhibitory immunoglobulin-like receptor containing an ITIM, is expressed on mast cells (MCs) and inhibits IgE-mediated anaphylaxis in mice. Here, we show that Allergin-1 inhibits TLR2-mediated activation of, and inflammatory cytokine production by, MCs in vitro Compared with wild-type mice, Allergin-1-deficient mice showed enhanced ear swelling with enhanced collagen deposition and greater Ly6G(+) neutrophil recruitment after intra-dermal injection of Pam2CSK4 into pinnae...
November 8, 2016: International Immunology
https://www.readbyqxmd.com/read/27930350/toll-like-receptor-tlr-4-and-myd88-are-essential-for-atheroprotection-by-peritoneal-b1a-b-cells
#5
Hamid Hosseini, Yi Li, Peter Kanellakis, Christopher Tay, Anh Cao, Edgar Liu, Karlheinz Peter, Peter Tipping, Ban-Hock Toh, Alex Bobik, Tin Kyaw
BACKGROUND: We previously identified peritoneal B1a cells that secrete natural IgM as a key atheroprotective B cell subset. However, the molecules that activate atheroprotective B1a cells are unknown. Here, we investigated whether Toll-like receptors (TLRs) TLR2, TLR4, and TLR9 expressed by B1a cells are required for IgM-mediated atheroprotection. METHODS AND RESULTS: We adoptively transferred B1a cells from wild-type mice or from mice deficient in TLR2, TLR4, TLR9, or myeloid differentiation primary response 88 (MyD88) into ApoE(-/-) mice depleted of peritoneal B1a cells by splenectomy and fed a high-fat diet for 8 weeks...
November 14, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27928019/tlr2-ligation-enhances-hiv-1-replication-in-activated-ccr6-cd4-t-cells-by-increasing-virus-entry-and-establishing-a-more-permissive-environment-to-infection
#6
Jean-François Bolduc, Michel Ouellet, Laurent Hany, Michel J Tremblay
: In this study, we investigated the effect of TLR2 ligation on the permissiveness of activated CD4(+) T cells to HIV-1 infection by focusing our experiments on the relative susceptibility of cell subsets based on their expression of CCR6. Purified primary human CD4(+) T cells were first subjected to a CD3/CD28 costimulation before treatment with the TLR2 agonist Pam3CSK4. Finally, cells were inoculated with R5-tropic HIV-1 particles that permit to study the effect of TLR2 triggering on virus production at both population and single-cell levels...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27925202/calprotectin-induces-il-6-and-mcp-1-production-via-toll-like-receptor-4-signaling-in-human-gingival-fibroblasts
#7
Yasufumi Nishikawa, Yukari Kajiura, Jung Hwan Lew, Jun-Ichi Kido, Toshihiko Nagata, Koji Naruishi
Calprotectin, a heterodimer of S100A8 and S100A9 molecules, is associated with inflammatory diseases such as inflammatory bowel disease. We have reported that calprotectin levels in gingival crevicular fluids of periodontitis patients are significantly higher than in healthy subjects. However, the functions of calprotectin in pathophysiology of periodontitis are still unknown. The aim of this study is to investigate the effects of calprotectin on the productivity of inflammatory cytokines in human gingival fibroblasts (HGFs)...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924359/effects-of-4-methylumbelliferone-and-high-molecular-weight-hyaluronic-acid-on-the-inflammation-of-corneal-stromal-cells-induced-by-lps
#8
Fang Li, Peng Hao, Guangjie Liu, Weiyi Wang, Ruifang Han, Zhixin Jiang, Xuan Li
PURPOSE: To investigate the effects of hyaluronic acid (HA) on the inflammation of corneal fibroblasts induced by lipopolysaccharide (LPS). METHODS: Primary rabbit corneal keratocytes were isolated with collagenase. The keratocytes were cultured in a serum-containing medium to induce corneal fibroblasts, which represented the wound repair phenotype of corneal keratocytes. Corneal fibroblasts were treated with LPS with or without 4-methylumbelliferone (4-MU) / high molecular weight hyaluronic acid (HMWHA)...
December 6, 2016: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/27920557/effect-of-smoking-on-the-genetic-makeup-of-toll-like-receptors-2-and-6
#9
Muhammad Kohailan, Mohammad Alanazi, Mahmoud Rouabhia, Abdullah Alamri, Narasimha Reddy Parine, Abdullah Alhadheq, Santhosh Basavarajappa, Abdul Aziz Abdullah Al-Kheraif, Abdelhabib Semlali
BACKGROUND: Cigarette smoking is a major risk factor for lung cancer, asthma, and oral cancer, and is central to the altered innate immune responsiveness to infection. Many hypotheses have provided evidence that cigarette smoking induces more genetic changes in genes involved in the development of many cigarette-related diseases. This alteration may be from single-nucleotide polymorphisms (SNPs) in innate immunity genes, especially the toll-like receptors (TLRs). OBJECTIVE: In this study, the genotype frequencies of TLR2 and TLR6 in smoking and nonsmoking population were examined...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27920273/divergent-functions-of-tlr2-on-hematopoietic-and-nonhematopoietic-cells-during-chronic-mycobacterium-tuberculosis-infection
#10
Jill Konowich, Archana Gopalakrishnan, Jillian Dietzold, Sheetal Verma, Kamlesh Bhatt, Wasiulla Rafi, Padmini Salgame
We have reported that TLR2 is crucial for host resistance against chronic Mycobacterium tuberculosis infection; however, which cell types are key players in this response remain unknown. This led us to decipher the relative contribution of TLR2 on nonhematopoietic and hematopoietic cells in resistance against chronic M. tuberculosis infection in mice infected with M. tuberculosis Erdman. Consistent with our previous report, at 8 wk of infection, TLR2 knockout (TLR2KO)→TLR2KO bone marrow chimeric mice exhibited increased bacterial burden, disorganized accumulation of lymphocytes and mononuclear cells, and extensive pulmonary immunopathology compared with wild-type (WT)→WT chimeric mice...
December 5, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27917375/recombinant-lipoprotein-rv1016c-derived-from-mycobacterium-tuberculosis-is-a-tlr-2-ligand-that-induces-macrophages-apoptosis-and-inhibits-mhc-ii-antigen-processing
#11
Haibo Su, Shenglin Zhu, Lin Zhu, Wei Huang, Honghai Wang, Zhi Zhang, Ying Xu
TLR2-dependent cellular signaling in Mycobacterium tuberculosis-infected macrophages causes apoptosis and inhibits class II major histocompatibility complex (MHC-II) molecules antigen processing, leading to evasion of surveillance. Mycobacterium tuberculosis (MTB) lipoproteins are an important class of Toll-like receptor (TLR) ligand, and identified as specific components that mediate these effects. In this study, we identified and characterized MTB lipoprotein Rv1016c (lpqT) as a cell wall associated-protein that was exposed on the cell surface and enhanced the survival of recombinants M...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27916353/toll-like-receptor-responses-are-suppressed-in-trauma-icu-patients
#12
Travis L Holloway, Susannah E Nicholson, Meenakshi Rani, Andrew P Cap, Martin G Schwacha
BACKGROUND: Inflammation and activation of the innate immune system are often associated with traumatic injury and may involve alterations in toll-like receptor (TLR)-mediated responses. METHODS: A prospective observational study was designed and conducted. Twenty-one severely injured (ISS = 16-41) trauma intensive care unit (ICU) patients and six healthy volunteers that served as controls were enrolled. Anticoagulated whole blood was collected at 2-12 d after ICU admission and incubated in the presence of media alone (baseline), zymosan (TLR2 agonist) or lipopolysaccharide (LPS; TLR4 agonist) for 3 h...
November 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27914450/mechanisms-of-inflammatory-injury-of-renal-tubular-cells-in-a-cellular-model-of-pyelonephritis
#13
M A Morosanova, E Y Plotnikov, L D Zorova, I B Pevzner, V A Popkov, D N Silachev, S S Jankauskas, V A Babenko, D B Zorov
Previously, we have assembled a cellular model of pyelonephritis which contains a primary culture of renal tubular epithelial cells, mononuclear leukocytes, and bacterial lysate or lipopolysaccharide. After cocultivation of renal cells with leukocytes and bacterial lysate, proinflammatory changes were observed in the renal cells, followed by nitrosative and oxidative stress and cell death. The interaction of bacterial antigens not only with leukocytes, but also with epithelial cells of the renal tubules, was partially mediated by signaling pathways involving Toll-like receptors (TLR2 and TLR4)...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27913794/tlr-ligands-but-not-modulators-of-histone-modifiers-can-induce-the-complex-immune-response-pattern-of-endotoxin-tolerance-in-mammary-epithelial-cells
#14
Juliane Günther, Wolfram Petzl, Holm Zerbe, Hans-Joachim Schuberth, Hans-Martin Seyfert
Excessive stimulation of the TLR4 axis through LPS reduces the expression of some cytokine genes in immune cells, while stimulating the expression of immune defense genes during a subsequent bacterial infection. This endotoxin tolerance (ET) is mediated via epigenetic mechanisms. Priming the udder of cows with LPS was shown to induce ET in mammary epithelial cells (MEC), thereby protecting the udder against reinfection for some time. Seeking alternatives to LPS priming we tried to elicit ET by priming MEC with either lipopeptide (Pam2CSK4) via the TLR2/6 axis or inhibitors of histone-modifying enzymes...
December 1, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27913793/inflammatory-signaling-pathways-induced-by-helicobacter-pylori-in-primary-human-gastric-epithelial-cells
#15
Cong Tri Tran, Magali Garcia, Martine Garnier, Christophe Burucoa, Charles Bodet
Inflammatory signaling pathways induced by Helicobacter pylori remain unclear, having been studied mostly on cell-line models derived from gastric adenocarcinoma with potentially altered signaling pathways and nonfunctional receptors. Here, H. pylori-induced signaling pathways were investigated in primary human gastric epithelial cells. Inflammatory response was analyzed on chemokine mRNA expression and production after infection of gastric epithelial cells by H. pylori strains, B128 and B128ΔcagM, a cag type IV secretion system defective strain...
December 1, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27912071/classical-and-alternative-macrophages-have-impaired-function-during-acute-and-chronic-hiv-1-infection
#16
Leonardo J Galvão-Lima, Milena S Espíndola, Luana S Soares, Fabiana A Zambuzi, Maira Cacemiro, Caroline Fontanari, Valdes R Bollela, Fabiani G Frantz
OBJECTIVES: Three decades after HIV recognition and its association with AIDS development, many advances have emerged - especially related to prevention and treatment. Undoubtedly, the development of Highly Active Antiretroviral Therapy (HAART) dramatically changed the future of the syndrome that we know today. In the present study, we evaluate the impact of HAART on macrophage function and its relevance to HIV pathogenesis. METHODS: PBMCs were isolated from blood samples and monocytes (CD14+ cells) were purified...
November 29, 2016: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27909766/association-between-tlr2-tlr4-gene-polymorphisms-and-copd-phenotype-in-a%C3%A2-greek-cohort
#17
A Apostolou, T Kerenidi, A Michopoulos, K I Gourgoulianis, M Noutsias, A E Germenis, M Speletas
BACKGROUND: Considering that the innate immune system plays a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD), we hypothesized that functional single-nucleotide polymorphisms (SNPs) of innate immune genes affect the disease phenotype and prognosis. AIM: To elucidate the contribution of common functional TLR2 and TLR4 SNPs and genotypic deficiency of the mannose-binding lectin (MBL) protein, both as single parameters and in combination, in Greek COPD patients...
December 1, 2016: Herz
https://www.readbyqxmd.com/read/27909057/structure-of-the-tir-domain-of-bcap-which-links-phosphoinositide-metabolism-with-the-negative-regulation-of-the-tlr-signalosome
#18
Samer Halabi, Eiki Sekine, Brett Verstack, Nicholas J Gay, Martin C Moncrieffe
Ligand binding to Toll-like receptors (TLRs) results in dimerization of their cytosolic TIR domains and recruitment of post-receptor signal transducers into a complex signalosome. TLR activation leads to the production of transcription factors, pro-inflammatory molecules and the activation of Phosphoinositide 3-kinases (PI3K) in a process that requires the multi-modular B-cell Adaptor for Phosphoinositide 3-kinase (BCAP). BCAP has a sequence previously proposed as a "cryptic" TIR domain. Here, we present the structure of the N-terminal region of human BCAP and show that it possesses a canonical TIR-fold...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27905994/the-role-of-il-10-in-mycobacterium-avium-subsp-paratuberculosis-infection
#19
REVIEW
Tariq Hussain, Syed Zahid Ali Shah, Deming Zhao, Srinand Sreevatsan, Xiangmei Zhou
Mycobacterium avium subsp. paratuberculosis (MAP) is an intracellular pathogen and is the causative agent of Johne's disease of domestic and wild ruminants. Johne's disease is characterized by chronic granulomatous enteritis leading to substantial economic losses to the livestock sector across the world. MAP persistently survives in phagocytic cells, most commonly in macrophages by disrupting its early antibacterial activity. MAP triggers several signaling pathways after attachment to pathogen recognition receptors (PRRs) of phagocytic cells...
December 1, 2016: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/27904654/augmentation-of-histone-deacetylase-3-hdac3-epigenetic-signature-at-the-interface-of-proinflammation-and-insulin-resistance-in-patients-with-type-2-diabetes
#20
Chandrakumar Sathishkumar, Paramasivam Prabu, Mahalingam Balakumar, Raji Lenin, Durai Prabhu, Ranjith Mohan Anjana, Viswanathan Mohan, Muthuswamy Balasubramanyam
BACKGROUND: A role of proinflammation has been implicated in the pathogenesis of diabetes, but the up-stream regulatory signals and molecular signatures are poorly understood. While histone modifications such as changes in histone deacetylase (HDAC) are emerging as novel epigenetic biomarkers, there is lack of studies to demonstrate their clinical relevance in diabetes. Therefore, we investigated the extent of HDAC machinery and inflammatory signals in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes mellitus (T2DM) compared to control subjects...
2016: Clinical Epigenetics
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