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https://www.readbyqxmd.com/read/29353304/unraveling-the-heterogeneity-of-igm-monoclonal-gammopathies-a-gene-mutational-and-gene-expression-study
#1
Cristina Jiménez, María Isabel Prieto-Conde, María García-Álvarez, Miguel Alcoceba, Fernando Escalante, María Del Carmen Chillón, Alfonso García de Coca, Ana Balanzategui, Alberto Cantalapiedra, Carlos Aguilar, Rocío Corral, Tomás González-López, Luis A Marín, Abelardo Bárez, Noemí Puig, Aránzazu García-Mateo, Norma C Gutiérrez, María Eugenia Sarasquete, Marcos González, Ramón García-Sanz
Immunoglobulin M (IgM) monoclonal gammopathies show considerable variability, involving three different stages of presentation: IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), asymptomatic Waldenström's macroglobulinemia (AWM), and symptomatic WM (SWM). Despite recent findings about the genomic and transcriptomic characteristics of such disorders, we know little about the causes of this clinical heterogeneity or the mechanisms involved in the progression from indolent to symptomatic forms...
January 20, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29353155/isolation-purification-structural-characterization-and-immunostimulatory-activity-of-water-soluble-polysaccharides-from-lepidium-meyenii
#2
Zhengqi Zha, Su-Yan Wang, Weihua Chu, Yang Lv, Hongjin Kan, Qiuli Chen, Lili Zhong, Long Yue, Jinna Xiao, Ying Wang, Hongping Yin
A water-soluble polysaccharide LMP-1 was isolated and purified by ion-exchange chromatography from maca (Lepidium meyenii Walp.). LMP-1 has a molecular weight of 1.01 × 104 Da, and is composed of glucose and arabinose with a molar ratio of 7.03:1.08. Methylation and the 1D and 2D NMR spectroscopy of LMP-1 revealed that it is mainly composed of →4)-α-D-Glcp-(1→, →6)-α-D-Glcp-(1→, →3)-α-D-Glcp-(1→, and β-D-Araf-(1→, with branching at O-6 of →4,6)-α-D-Glcp-(1 → . LMP-1 showed up-regulation of Toll-like receptor 4 (TLR4) and Toll-like receptor 2 (TLR2)...
January 17, 2018: Phytochemistry
https://www.readbyqxmd.com/read/29352876/structural-characterization-and-macrophage-activation-of-a-hetero-galactan-isolated-from-flammulina-velutipes
#3
Yue Meng, Jingmin Yan, Guang Yang, Zhen Han, Guihua Tai, Hairong Cheng, Yifa Zhou
We isolated and purified a new polysaccharide (WFVP-N-b1) with a molecular weight of 20 kDa from Flammulina velutipes. Results showed that WFVP-N-b1 is composed of an α (1 → 6)-linked D-galactan backbone and branched at the O-2 of its Galp residues by an α-D-(1 → 6)-linked Manp attached to t-β-D-Glcp or t-α-D-Fucp side chains. WFVP-N-b1 can significantly induce cytokines secretion and release of toxic molecules. On a cellular level, WFVP-N-b1 is recognized by Toll-like receptor 4 (TLR4). Thereby, the hetero-galactan increased the phosphorylation of mitogen-activated protein kinases (MAPKs) and Akt, promoted degradation of IκB-α and the nuclear translocation of the NF-κB p65 subunit...
March 1, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29352108/desumoylation-of-mkk7-kinase-by-the-sumo2-3-protease-senp3-potentiates-lipopolysaccharide-induced-inflammatory-signaling-in-macrophages
#4
Yimin Lao, Kai Yang, Zhaojun Wang, Xueqing Sun, Qiang Zou, Xiaoyan Yu, Jinke Cheng, Xuemei Tong, Edward Th Yeh, Jie Yang, Jing Yi
Protein SUMOylation has been reported to play a role in innate immune response, but the enzymes, substrates, and consequences of the specific inflammatory signaling events are largely unknown. Reactive oxygen species (ROS) are abundantly produced during macrophage activation and required for Toll-like receptor 4 (TLR4)-mediated inflammatory signaling. Previously, we demonstrated that SENP3 is a redox-sensitive SUMO2/3 protease. To explore any links between reversible SUMOylation and ROS-related inflammatory signaling in macrophage activation, we generated mice with SENP3 conditional knockout in myeloid cells...
January 19, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29351737/identifying-genome-wide-immune-gene-variation-underlying-infectious-disease-in-wildlife-populations-a-next-generation-sequencing-approach-in-the-gopher-tortoise
#5
Jean P Elbers, Mary B Brown, Sabrina S Taylor
BACKGROUND: Infectious disease is the single greatest threat to taxa such as amphibians (chytrid fungus), bats (white nose syndrome), Tasmanian devils (devil facial tumor disease), and black-footed ferrets (canine distemper virus, plague). Although understanding the genetic basis to disease susceptibility is important for the long-term persistence of these groups, most research has been limited to major-histocompatibility and Toll-like receptor genes. To better understand the genetic basis of infectious disease susceptibility in a species of conservation concern, we sequenced all known/predicted immune response genes (i...
January 19, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29351447/cigarette-smoke-dampens-anti-viral-signaling-in-small-airway-epithelial-cells-by-disrupting-tlr3-cleavage
#6
Parker F Duffney, Claire E McCarthy, Aitor Nogales, Thomas H Thatcher, Luis Martinez-Sobrido, Richard P Phipps, Patricia J Sime
Cigarette smokers and people exposed to secondhand smoke are at an increased risk for pulmonary viral infections, yet the mechanism responsible for this heightened susceptibility is not understood. To understand the effect of cigarette smoke on susceptibility to viral infection we used an air-liquid interface culture system, and exposed primary human small airway epithelial cells (SAEC) to whole cigarette smoke followed by treatment with the viral mimetic polyinosinic polycytidylic acid (poly I:C) or influenza A virus (IAV)...
December 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351083/transcriptional-analysis-of-immune-relevant-genes-in-the-mucus-of-labeo-rohita-experimentally-infected-with-argulus-siamensis
#7
Sonali Parida, Amruta Mohapatra, Banya Kar, Jyotirmaya Mohanty, Pramoda Kumar Sahoo
The knowledge of mucosa-associated molecular events that occur during infections is scarce despite the well-established importance of mucus in fish immunity. Using qRT-PCR, we analyzed the immune gene expression patterns in mucus of Labeo rohita experimentally infected with an ectoparasite Argulus siamensis. Mucus samples were collected at 0 h, 12 h, 24 h, 3 d, 7 d, 15 d, and 30 d post challenge of L. rohita with metanauplii of A. siamensis. All interleukins studied herein (IL 6, IL 15, and IL 1β) showed significant upregulation of expression levels in mucus of A...
March 26, 2018: Acta Parasitologica
https://www.readbyqxmd.com/read/29350898/identification-of-individual-bacterial-cells-through-the-intermolecular-interactions-with-peptide-functionalized-solid-state-pores
#8
Makusu Tsutsui, Masayoshi Tanaka, Takahiro Marui, Kazumichi Yokota, Takeshi Yoshida, Akihide Arima, Wataru Tonomura, Masateru Taniguchi, Takashi Washio, Mina Okochi, Tomoji Kawai
Bioinspired pore sensing for selective detection of flagellated bacteria was investigated. The Au micropore wall surface was modified with a synthetic peptide designed from toll-like receptor 5 (TLR5) to mimic the pathogen-recognition capability. We found that intermolecular interactions between the TLR5-derived recognition peptides and flagella induce ligand-specific perturbations in the translocation dynamics of Escherichia coli, which facilitated the discrimination between the wild-type and flagellin-deletion mutant (ΔfliC) by the resistive pulse patterns thereby demonstrating the sensing of bacteria at a single-cell level...
January 19, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29350750/the-hepatoprotective-effect-of-selenium-enriched-yeast-and-gum-arabic-combination-on-carbon-tetrachloride-induced-chronic-liver-injury-in-rats
#9
Mohammed Hamid, Yassin Abdulrahim, Dandan Liu, Gang Qian, Alamzeb Khan, Kehe Huang
The antioxidant and anti-inflammatory effects of selenium-enriched yeast (SY) and Gum Arabic (GA) have been reported. This study aimed to determine the hepatoprotective effect of SY and GA combination on carbon tetrachloride (CCl4 )-induced chronic liver injury in rats and to explore their synergistic mechanisms of action. Forty adult male Wistar rats randomly allotted to 5 groups: (A) worked as control, (B) was administered CCl4 , (C-E) were fed daily by GA, SY, and GA+SY respectively after mixing with basal diet, following CCl4 -intoxication...
January 19, 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29348888/the-association-analysis-of-tlr2-and-tlr4-gene-with-tuberculosis-in-the-tibetan-chinese-population
#10
Xin Xue, Yi Qiu, Dong Jiang, Tianbo Jin, Mengdan Yan, Xikang Zhu, Yonglie Chu
Background: The present study was undertaken to explore the relationship of Toll-like receptor (TLR) 2, TLR4 genes polymorphisms with Pulmonary tuberculosis (PTB) risk in a sample of Chinese population. Methods: For this study, we recruited 467 subjects with PTB and 504 healthy subjects from a Tibetan population living in near or in Xi'an, China. Association analyses of single-nucleotide polymorphisms (SNPs) in TLR2 and TLR4 were performed with SPSS Statistics (version 17...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348435/macrophage-sensing-of-single-walled-carbon-nanotubes-via-toll-like-receptors
#11
Sourav P Mukherjee, Olesja Bondarenko, Pekka Kohonen, Fernando T Andón, Táňa Brzicová, Isabel Gessner, Sanjay Mathur, Massimo Bottini, Paolo Calligari, Lorenzo Stella, Elena Kisin, Anna Shvedova, Reija Autio, Heli Salminen-Mankonen, Riitta Lahesmaa, Bengt Fadeel
Carbon-based nanomaterials including carbon nanotubes (CNTs) have been shown to trigger inflammation. However, how these materials are 'sensed' by immune cells is not known. Here we compared the effects of two carbon-based nanomaterials, single-walled CNTs (SWCNTs) and graphene oxide (GO), on primary human monocyte-derived macrophages. Genome-wide transcriptomics assessment was performed at sub-cytotoxic doses. Pathway analysis of the microarray data revealed pronounced effects on chemokine-encoding genes in macrophages exposed to SWCNTs, but not in response to GO, and these results were validated by multiplex array-based cytokine and chemokine profiling...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348414/microrna-146a-5p-attenuates-irradiation-induced-and-lps-induced-hepatic-stellate-cell-activation-and-hepatocyte-apoptosis-through-inhibition-of-tlr4-pathway
#12
Yuhan Chen, Zhifeng Wu, Baoying Yuan, Yinying Dong, Li Zhang, Zhaochong Zeng
Elevated toll-like receptor 4 (TLR4) expression is associated with a high risk of radiation-induced liver disease (RILD). MicroRNA (miR)-146a-5p is a key regulator of lipopolysaccharide (LPS)/TLR4 signaling, but its role in modulation of RILD remains unclear. Here, we found that irradiation and LPS stimulation induced TLR4 and miR-146a-5p expression in the human hepatic stellate cell (HSC) line LX2. Ectopic expression of miR-146a-5p in LX2 inhibited irradiation-induced and LPS-induced pro-inflammatory cytokine secretion and cell proliferation, and promoted cell apoptosis by down-regulating the expression levels of TLR4, interleukin-1 receptor associated kinase 1 (IRAK1), tumor necrosis factor receptor associated factor 6 (TRAF6) and phosphorylation of nuclear factor-kappa B...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348267/toll-like-receptor-9-dependent-ampk%C3%AE-activation-occurs-via-tak1-and-contributes-to-rhoa-rock-signaling-and-actin-polymerization-in-vascular-smooth-muscle-cells
#13
Cameron G McCarthy, Camilla Ferreira Wenceslau, Safia Ogbi, Theodora Szasz, R Clinton Webb
Traditionally, Toll-like receptor (TLR)9 signals through a MyD88-dependent cascade that results in pro-inflammatory gene transcription. Recently it was reported that TLR9 also participates in a stress tolerance signaling cascade in non-immune cells. In this non-canonical pathway, TLR9 binds to and inhibits sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2), modulating intracellular calcium handling, and subsequently resulting in the activation of 5'-AMP-activated protein kinase (AMPK)α. We have previously reported TLR9 causes increased contraction in isolated arteries; however, the mechanisms underlying this vascular dysfunction need to be further clarified...
January 18, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29348256/flavonoids-dairy-foods-and-cardiovascular-and-metabolic-health-a-review-of-emerging-biologic-pathways
#14
REVIEW
Dariush Mozaffarian, Jason H Y Wu
A growing body of nutritional science highlights the complex mechanisms and pleiotropic pathways of cardiometabolic effects of different foods. Among these, some of the most exciting advances are occurring in the area of flavonoids, bioactive phytochemicals found in plant foods; and in the area of dairy, including milk, yogurt, and cheese. Many of the relevant ingredients and mechanistic pathways are now being clarified, shedding new light on both the ingredients and the pathways for how diet influences health and well-being...
January 19, 2018: Circulation Research
https://www.readbyqxmd.com/read/29345364/the-n-terminal-peptide-moiety-of-the-mycobacterium-tuberculosis-19-kda-lipoprotein-harbors-rp105-agonistic-properties
#15
Thomas E Schultz, Karl-Heinz Wiesmüller, Megan Lucas, Karen M Dobos, Alan G Baxter, Antje Blumenthal
Radioprotective 105 kDa (RP105, CD180) is a member of the Toll-like receptor (TLR) family that interacts with TLR2 and facilitates recognition of mature lipoproteins expressed by Mycobacterium tuberculosis and Mycobacterium bovis BCG. In this study, we used synthetic lipopeptide analogs of the M. tuberculosis 19 kDa lipoprotein to define structural characteristics that promote RP105-mediated host cell responses. A tripalmitoylated lipopeptide composed of the first 16 N-terminal amino acids of the M. tuberculosis 19 kDa lipoprotein induced RP105-dependent TNF and IL-6 production by macrophages...
January 9, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345344/differential-outcomes-of-tlr2-engagement-in-inflammation-induced-preterm-birth
#16
Monica Cappelletti, Matthew J Lawson, Calvin C Chan, Adrienne N Wilburn, Senad Divanovic
Preterm birth (PTB) is the leading cause of neonatal mortality worldwide. Infection and inflammation are considered main causes of PTB. Among multiple pathogens, Gram-positive bacteria are commonly linked with induction of PTB. Although activation of innate immune responses, via TLR2 engagement, by Gram-positive bacteria is a likely cause, whether induction of PTB depends on the potency of specific microbial components to induce Toll-like receptor (TLR)2-driven inflammation has not been elucidated. Here, we show that TLR2 activation by synthetic lipopeptides, Pam2Cys, and Pam3Cys specifically, variably influenced inflammation and subsequent induction of PTB...
December 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345056/for-when-bacterial-infections-persist-toll-like-receptor-inducible-direct-antimicrobial-pathways-in-macrophages
#17
REVIEW
Claudia J Stocks, Mark A Schembri, Matthew J Sweet, Ronan Kapetanovic
Macrophages are linchpins of innate immunity, responding to invading microorganisms by initiating coordinated inflammatory and antimicrobial programs. Immediate antimicrobial responses, such as NADPH-dependent reactive oxygen species (ROS), are triggered upon phagocytic receptor engagement. Macrophages also detect and respond to microbial products through pattern recognition receptors (PRRs), such as TLRs. TLR signaling influences multiple biological processes including antigen presentation, cell survival, inflammation, and direct antimicrobial responses...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29343779/characterization-of-signaling-pathways-regulating-the-expression-of-pro-inflammatory-long-form-thymic-stromal-lymphopoietin-upon-human-metapneumovirus-infection
#18
Youxian Li, Cecilie Lund, Ida Nervik, Simon Loevenich, Henrik Døllner, Marit W Anthonsen, Ingvild B Johnsen
Thymic stromal lymphopoietin (TSLP) is associated with several allergic diseases including asthma. Two isoforms of TSLP exist in humans, a long form (lfTSLP) and a short form (sfTSLP), displaying distinct immunological functions. Recently, TSLP was found to be upregulated in human airway cells upon human metapneumovirus (hMPV) infection, yet it remains unclear if the two isoforms are regulated differently during hMPV infection. Importantly, the molecular mechanisms underlying hMPV-mediated TSLP induction remain undescribed...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343725/the-phosphatase-ppm1a-controls-monocyte-to-macrophage-differentiation
#19
Samuel R Smith, Kaitlyn Schaaf, Nusrah Rajabalee, Frederic Wagner, Alexandra Duverger, Olaf Kutsch, Jim Sun
Differentiation of circulating monocytes into tissue-bound or tissue-resident macrophages is a critical regulatory process affecting host defense and inflammation. However, the regulatory signaling pathways that control the differentiation of monocytes into specific and distinct functional macrophage subsets are poorly understood. Herein, we demonstrate that monocyte-to-macrophage differentiation is controlled by the Protein Phosphatase, Mg2+/Mn2+-dependent 1A (PPM1A). Genetic manipulation experiments demonstrated that overexpression of PPM1A attenuated the macrophage differentiation program, while knockdown of PPM1A expression accelerated the ability of monocytes to differentiate into macrophages...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343440/chanzyme-trpm7-mediates-the-ca2-influx-essential-for-lipopolysaccharide-induced-toll-like-receptor-4-endocytosis-and-macrophage-activation
#20
Michael S Schappe, Kalina Szteyn, Marta E Stremska, Suresh K Mendu, Taylor K Downs, Philip V Seegren, Michelle A Mahoney, Sumeet Dixit, Julia K Krupa, Eric J Stipes, Jason S Rogers, Samantha E Adamson, Norbert Leitinger, Bimal N Desai
Toll-like receptors (TLRs) sense pathogen-associated molecular patterns to activate the production of inflammatory mediators. TLR4 recognizes lipopolysaccharide (LPS) and drives the secretion of inflammatory cytokines, often contributing to sepsis. We report that transient receptor potential melastatin-like 7 (TRPM7), a non-selective but Ca2+-conducting ion channel, mediates the cytosolic Ca2+ elevations essential for LPS-induced macrophage activation. LPS triggered TRPM7-dependent Ca2+ elevations essential for TLR4 endocytosis and the subsequent activation of the transcription factor IRF3...
January 16, 2018: Immunity
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