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https://www.readbyqxmd.com/read/28634370/microbial-antigens-stimulate-metalloprotease-7-secretion-in-human-b-lymphocytes-using-mtor-dependent-and-independent-pathways
#1
Mohamed F Ali, Harika Dasari, Virginia P Van Keulen, Divi Cornec, George Vasmatzis, Tobias Peikert, Eva M Carmona
Metalloproteinases (MMPs) contribute to tissue remodeling and acute inflammation not only by degrading extracellular matrix proteins but also by controlling the influx of chemokines through the regulation and shedding of syndecans. B-lymphocytes, in addition to their well-known function as antibody producing cells, participate in the innate immune response by secreting inflammatory cytokines and chemokines. However, there is little information about the role of B-lymphocytes in the regulation of MMPs; consequently, herein we investigated whether activated human circulating B-lymphocytes contributed to the secretion of MMPs...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28626065/metabolic-reprogramming-commits-differentiation-of-human-cd27-igd-b-cells-to-plasmablasts-or-cd27-igd-cells
#2
Masataka Torigoe, Shigeru Iwata, Shingo Nakayamada, Kei Sakata, Mingzeng Zhang, Maiko Hajime, Yusuke Miyazaki, Manabu Narisawa, Koji Ishii, Hirotaka Shibata, Yoshiya Tanaka
B cells play a crucial role in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE). However, the relevance of the metabolic pathway in the differentiation of human B cell subsets remains unknown. In this article, we show that the combination of CpG/TLR9 and IFN-α markedly induced the differentiation of CD27(+)IgD(+) unswitched memory B cells into CD27(hi)CD38(hi) plasmablasts. The response was accompanied by mammalian target of rapamycin complex 1 (mTORC1) activation and increased lactate production, indicating a shift to glycolysis...
June 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28624699/toll-like-receptor-2-rs4696480-polymorphism-and-risk-of-oral-cancer-and-oral-potentially-malignant-disorder
#3
Camila de Barros Gallo, Xabier Marichalar-Mendia, Amaia Setien-Olarra, Amelia Acha-Sagredo, Naiara Garcia Bediaga, Maria Luisa Gainza-Cirauqui, Norberto Nobuo Sugaya, Jose Manuel Aguirre-Urizar
OBJECTIVES: The aim of this study was to identify the possible association between TLR polymorphisms and an increased risk of developing head and neck cancer, including oral (OSCC) and laryngeal squamous cell carcinoma (LSCC), and oral potentially malignant disorders, such as oral lichenoid disease (OLD), including oral lichen planus (OLP) and oral lichenoid lesions (OLL). DESIGN: This case-control study included 40 OSCC, 35 LSCC, 175 OLD (129 OLP and 46 OLL) patients and 89 healthy controls, all of them from the Basque Country, Spain...
June 6, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28620261/single-nucleotide-polymorphism-based-genetic-diversity-analysis-of-the-kilakarsal-and-vembur-sheep-breeds
#4
Rathinasamy Selvam, Nagarajan Murali, A Kannan Thiruvenkadan, Ramesh Saravanakumar, Gurusamy Ponnudurai, Thilak Pon Jawahar
AIM: The present study was thus undertaken to analyze the genetic diversity of Kilakarsal and Vembur sheep breeds using single-nucleotide polymorphism (SNP) markers within Toll-like receptor (TLR) 3, 5, 6, 9, and 10 genes. MATERIALS AND METHODS: Competitive allele-specific polymerase chain reaction (PCR)-based end-point genotyping was performed using real-time PCR to type the SNPs. Allele discrimination module implemented in real-time PCR was utilized to call the genotypes based on fluorescence intensity recorded for each of the two alleles...
May 2017: Veterinary World
https://www.readbyqxmd.com/read/28618428/the-impact-of-circulating-mitochondrial-dna-on-cardiomyocyte-apoptosis-and-myocardial-injury-after-tlr4-activation-in-experimental-autoimmune-myocarditis
#5
Bangwei Wu, Huanchun Ni, Jian Li, Xinyu Zhuang, Jinjin Zhang, Zhiyong Qi, Qiying Chen, Zhichao Wen, Haiming Shi, Xinping Luo, Bo Jin
BACKGROUND/AIMS: Mitochondrial DNA (mtDNA), acting as a newly found 'danger-associated molecular patterns' (DAMPs), is released into circulation upon tissue injury and performs as a considerable activator of inflammation and immune response. However, the role of circulating mtDNA in experimental autoimmune myocarditis (EAM) as well as Toll like receptor4 (TLR4) mediated cardiac inflammation and injury remains unknown. METHODS: A model of EAM was established in BALB/c mice by immunization with porcine cardiac myosin...
June 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28617991/interferon-%C3%AE-regulates-the-production-of-il-10-by-toll-like-receptor-activated-microglia
#6
Diogo Lobo-Silva, Guilhermina M Carriche, A Gil Castro, Susana Roque, Margarida Saraiva
Pattern recognition receptors, such as toll-like receptors (TLRs), perceive tissue alterations and initiate local innate immune responses. Microglia, the resident macrophages of the brain, encode TLRs which primary role is to protect the tissue integrity. However, deregulated activation of TLRs in microglia may lead to chronic neurodegeneration. This double role of microglial responses is often reported in immune-driven neurologic diseases, as in multiple sclerosis (MS). Consequently, strategies to manipulate microglia inflammatory responses may help to ameliorate disease progression...
June 15, 2017: Glia
https://www.readbyqxmd.com/read/28615284/tcl1a-snps-and-estrogen-mediated-toll-like-receptor-myd88-dependent-nf-%C3%AE%C2%BAb-activation-snp-and-serm-dependent-modification-of-inflammation-and-immune-response
#7
Ming-Fen Ho, James N Ingle, Tim Bongartz, Krishna R Kalari, Paul E Goss, Lois E Shepherd, Taisei Mushiroda, Michiaki Kubo, Liewei Wang, Richard M Weinshilboum
In a previous genome-wide association study (GWAS) for musculoskeletal adverse events during aromatase inhibitor therapy of breast cancer, we reported that single nucleotide polymorphisms (SNPs) near the TCL1A gene were associated with this adverse drug reaction. Functional genomic studies showed that TCL1A expression was induced by estradiol (E2), but only in cells with the variant sequence for the top GWAS SNP (rs11849538), a SNP that created a functional estrogen response element. In addition, TCL1A genotype influenced the "downstream" expression of a series of cytokines and chemokines and had a striking effect on NF-κB transcriptional activity...
June 14, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28615131/stimulation-of-colorectal-biopsies-from-miniature-dachshunds-with-inflammatory-colorectal-polyps-with-toll-like-receptor-ligands-a-pilot-study
#8
Nozomu Yokoyama, Hiroshi Ohta, Yumiko Kagawa, Noriyuki Nagata, Khoirun Nisa, Tomoya Morita, Tatsuyuki Osuga, Noboru Sasaki, Keitaro Morishita, Kensuke Nakamura, Mitsuyoshi Takiguchi
Inflammatory colorectal polyps (ICRPs) in miniature dachshunds (MDs) are a possible novel form of breed-specific canine inflammatory bowel disease (IBD). In this pilot study, we investigated the effects of different Toll like receptor (TLR2, TLR4, TLR5 and TLR9) ligands on pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) gene expression in ex vivo-cultured colorectal samples from four MDs with ICRPs and four healthy MDs. At baseline, no significant difference in the mRNA expression levels of TLRs and pro-inflammatory cytokines was observed between cases and control MDs...
June 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28605247/the-distinct-and-cooperative-roles-of-toll-like-receptor-9-and-receptor-for-advanced-glycation-end-products-in-modulating-in-vivo-inflammatory-responses-to-select-cpg-and-non-cpg-oligonucleotides
#9
Suzanne Paz, Jill Hsiao, Patrick Cauntay, Armand Soriano, Lawrence Bai, Todd Machemer, Xiaokun Xiao, Shuling Guo, Gene Hung, Husam Younis, C Frank Bennett, Scott Henry, Theodore J Yun, Sébastien Burel
Antisense oligonucleotides (ASOs) are widely accepted therapeutic agents that suppress RNA transcription. While the majority of ASOs are well tolerated in vivo, few sequences trigger inflammatory responses in absence of conventional CpG motifs. In this study, we identified non-CpG oligodeoxy-nucleotide (ODN) capable of triggering an inflammatory response resulting in B cell and macrophage activation in a MyD88- and TLR9-dependent manner. In addition, we found the receptor for advance glycation end product (RAGE) receptor to be involved in the initiation of inflammatory response to suboptimal concentrations of both CpG- and non-CpG-containing ODNs...
June 12, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28600543/innate-and-adaptive-immunity-are-progressively-activated-in-parallel-with-renal-injury-in-the-5-6-renal-ablation-model
#10
Camilla Fanelli, Simone C A Arias, Flavia G Machado, Jessica K Okuma, Denise M A C Malheiros, Hatylas Azevedo, Carlos A Moreira-Filho, Niels O S Camara, Clarice K Fujihara, Roberto Zatz
The mechanisms triggering renal inflammation in chronic kidney disease (CKD) are unclear. We performed a detailed analysis of the time course of innate and adaptive immunity activation in the 5/6 renal ablation (Nx) model. Munich-Wistar rats undergoing Nx were studied 15, 60 and 120 days after ablation. Hypertension, albuminuria, creatinine retention, interstitial expansion and infiltration by macrophages and T-lymphocytes were already evident 15 days after Nx. PCR-array was used to screen for altered gene expression, whereas gene and protein expressions of TLR4, CASP1, IL-1β and NLRP3 were individually assessed...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28594360/rapid-complexation-of-aptamers-by-their-specific-antidotes
#11
Heidi Stoll, Heidrun Steinle, Nadja Wilhelm, Ludmilla Hann, Silju-John Kunnakattu, Miwako Narita, Christian Schlensak, Hans P Wendel, Meltem Avci-Adali
Nucleic acid ligands, aptamers, harbor the unique characteristics of small molecules and antibodies. The specificity and high affinity of aptamers enable their binding to different targets, such as small molecules, proteins, or cells. Chemical modifications of aptamers allow increased bioavailability. A further great benefit of aptamers is the antidote (AD)-mediated controllability of their effect. In this study, the AD-mediated complexation and neutralization of the thrombin binding aptamer NU172 and Toll-like receptor 9 (TLR9) binding R10-60 aptamer were determined...
June 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28592890/polymorphism-in-the-gene-encoding-toll-like-receptor-10-may-be-associated-with-asthma-after-bronchiolitis
#12
Sari Törmänen, Matti Korppi, Johanna Teräsjärvi, Juho Vuononvirta, Petri Koponen, Merja Helminen, Qiushui He, Kirsi Nuolivirta
Toll-like receptors (TLRs) recognise microbes that contribute to the severity of bronchiolitis and the subsequent risk of asthma. We evaluated whether post-bronchiolitis asthma was associated with polymorphisms in the TLR3 rs3775291, TLR4 rs4986790, TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084, and TLR10 rs4129009 genes. The gene polymorphisms were studied at the age of 6.4 years (mean) in 135 children hospitalised for bronchiolitis in infancy. The outcome measure was current or previous asthma. Current asthma was more common (30%) in children with the variant AG or GG genotype in the TLR10 rs4129009 gene versus those who were homozygous for the major allele A (11%) (p = 0...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592426/a-nonadjuvanted-igg2a-monoclonal-antibody-against-nucleosomes-elicits-potent-t-cell-dependent-idiotype-specific-igg1-responses-and-glomerular-igg1-igg2a-deposits-in-normal-mice
#13
Kristian Hannestad, Helge Scott
Idiotypes (Ids) are unique epitopes of Ab V regions and can trigger anti-Id immune responses, but immunization with several nonadjuvanted isologous IgG mAbs has induced tolerance to their Ids. We immunized non-lupus-prone mice with 11 allotype "a" of IgG2a (IgG2a(a)) and 4 IgG2c nonadjuvanted, isologous mAbs purified from serum-free medium. Of five IgG2a(a) mAbs with specificity for nucleosomes, the repeating histone-DNA subunit of chromatin, four elicited an IgG1 anti-mAb response and one mAb was nonimmunogenic...
June 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28577901/functional-studies-of-chronic-lymphocytic-leukemia-b-cells-expressing-%C3%AE-2-integrin-type-complement-receptors-cr3-and-cr4
#14
Barbara Uzonyi, Bernadett Mácsik-Valent, Szilvia Lukácsi, Richárd Kiss, Katalin Török, Mariann Kremlitzka, Zsuzsa Bajtay, Judit Demeter, Csaba Bödör, Anna Erdei
The expression and role of CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in B cells are not yet explored in contrast to myeloid cells, where these β2-integrin type receptors are known to participate in various cellular functions, including phagocytosis, adherence and migration. Here we aimed to reveal the expression and role of CR3 and CR4 in human B cells. In B cells of healthy donors CR3 and CR4 are scarcely expressed. However, two patients with chronic lymphocytic leukemia (CLL) characterized by a peculiar immune-phenotype containing both CD5-positive and CD5-negative B cell populations made possible to study these molecules in distinct B cell subsets...
May 31, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28576980/tlr9-regulates-the-nf-%C3%AE%C2%BAb-nlrp3-il-1%C3%AE-pathway-negatively-in-salmonella-induced-nkg2d-mediated-intestinal-inflammation
#15
Yan Li, Meifang Liu, Zengyan Zuo, Jing Liu, Xin Yu, Yun Guan, Renhui Zhan, Qiuju Han, Jian Zhang, Rongbin Zhou, Rui Sun, Zhigang Tian, Cai Zhang
TLRs are key sensors for conserved bacterial molecules and play a critical role in host defense against invading pathogens. Although the roles of TLRs in defense against pathogen infection and in maintaining gut immune homeostasis have been studied, the precise functions of different TLRs in response to pathogen infection in the gut remain elusive. The present study investigated the role of TLR signaling in defense against the Gram-negative bacterial pathogen Salmonella typhimurium The results indicated that TLR9-deficient mice were more susceptible to S...
June 2, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28574819/heat-killed-salmonella-typhimurium-hkst-protects-mice-against-radiation-in-tlr4-dependent-manner
#16
Yang Xu, Yuanyuan Chen, Hu Liu, Xiao Lei, Jiaming Guo, Kun Cao, Cong Liu, Bailong Li, Jianming Cai, Jintao Ju, Fu Gao, Yanyong Yang
It is urgently required to develop novel safe and effective radioprotectors to alleviate radiation damages. Recently, several toll like receptors (TLRs), including TLR2, TLR4, TLR5, TLR9, have been proved to exert protective effects against ionizing radiation. Due to different tissue-distribution and distinct functions of TLRs, we hypothesized that co-activation of multiple TLRs simultaneously may produce extensive and stronger radioprotective effects. In this study, we found the co-agonist of TLR2, TLR4 and TLR5, heat-killed Salmonella typhimurium (HKST) significantly inhibited radiation-induced cell apoptosis, increased cell survival and alleviated DNA damage...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28574818/characterization-of-the-release-and-biological-significance-of-cell-free-dna-from-breast-cancer-cell-lines
#17
Wei Wang, Peng Kong, Ge Ma, Li Li, Jin Zhu, Tiansong Xia, Hui Xie, Wenbin Zhou, Shui Wang
In breast cancer, cell-free DNA (cfDNA) has been proven to be a diagnostic and prognostic biomarker. However, there have been few studies on the origin and biological significance of cfDNA. In this study, we assessed the release pattern of cfDNA from breast cancer cell lines under different culture conditions and investigated the biological significance of cfDNA. The cfDNA concentration increased rapidly (6 h) after passage, decreased gradually, and was then maintained at a relatively stable level after 24 h...
May 15, 2017: Oncotarget
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
#18
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/28571545/potential-medications-or-compounds-acting-on-toll-like-receptors-in-cerebral-ischemia
#19
Man Li, Jing Liu, Ying Bi, Jixiang Chen, Lei Zhao
Toll-like receptors have been suggested to play an integral role in the process of inflammatory response after ischemic injury. Of all 9 TLRs presenting in brain, functions of TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9 have been studied in recent years. The MyD88 pathway and TIR domain-containing adaptor inducing interferon pathway are involved in these pathophysiological changes. Since the important role, the therapeutic potential of strategies acting on TLRs should be evaluated. Feasible approaches may function in the following respects, methods acting on TLRs directly, modulations of MyD88 or TRIF signaling pathway, and the ischemic tolerance induced by the preconditioning or postconditioning with TLR ligands or minor cerebral ischemia...
June 1, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28569041/predictive-value-of-tlr7-polymorphism-for-cetuximab-based-chemotherapy-in-patients-with-metastatic-colorectal-cancer
#20
Satoshi Okazaki, Sebastian Stintzing, Yu Sunakawa, Shu Cao, Wu Zhang, Dongyun Yang, Yan Ning, Satoshi Matsusaka, Martin D Berger, Yuji Miyamoto, Mitsukuni Suenaga, Marta Schirripa, Jordan D West, Roel Gopez, Tsuji Akihito, Wataru Ichikawa, Volker Heinemann, R William DePaolo, Heinz-Josef Lenz
The TLR7 and TLR9 signalings are implicated in the regulation of the immune system through type-I interferon induction. Preclinical studies have demonstrated the immunomodulatory and antitumor effects of TLR7 and TLR9 agonists in combination with cetuximab. We tested the hypothesis that genetic variations in TLR7 and TLR9 and their downstream molecules IRF5 and IRF7 were associated with outcomes in metastatic colorectal cancer (mCRC) patients receiving cetuximab-based chemotherapy. Six single nucleotide polymorphisms (SNPs) in TLR7, TLR9, IRF5 and IRF7 were tested for the association with RR, PFS, and OS in KRAS-wild type mCRC patients...
May 31, 2017: International Journal of Cancer. Journal International du Cancer
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