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https://www.readbyqxmd.com/read/28340358/lysosomal-rupture-induced-by-structurally-distinct-chitosans-either-promotes-a-type-1-ifn-response-or-activates-the-inflammasome-in-macrophages
#1
David Fong, Pascal Grégoire-Gélinas, Alexandre P Cheng, Tal Mezheritsky, Marc Lavertu, Sachiko Sato, Caroline D Hoemann
Chitosan is a family of glucosamine and N-acetyl glucosamine polysaccharides with poorly understood immune modulating properties. Here, functional U937 macrophage responses were analyzed in response to a novel library of twenty chitosans with controlled degree of deacetylation (DDA, 60-98%), molecular weight (1 to >100 kDa), and acetylation pattern (block vs. random). Specific chitosan preparations (10 or 190 kDa 80% block DDA and 3, 5, or 10 kDa 98% DDA) either induced macrophages to release CXCL10 and IL-1ra at 5-50 μg/mL, or activated the inflammasome to release IL-1β and PGE2 at 50-150 μg/mL...
March 15, 2017: Biomaterials
https://www.readbyqxmd.com/read/28336310/regulatory-role-of-ccl5-rs2280789-and-cxcl10-rs56061981-gene-polymorphisms-on-intracellular-ccl5-and-cxcl10-expression-in-pulmonary-tuberculosis
#2
Brijendra Singh, Selvaraj Anbalagan, Paramasivam Selvaraj
Genetic variations in chemokine genes influence the chemoattractive properties of T cells which may be associated with outcome of infections. In present study, we have investigated the regulatory role played by In1.1T/C (rs2280789) polymorphism of CCL5 and -135G/A (rs56061981) polymorphism of CXCL10 gene on intracellular CCL5 and CXCL10 expression in T cells. Whole blood cell cultures were stimulated with culture filtrate antigen (CFA) and infected with live M. tuberculosis were used for intracellular CCL5 and CXCL10 expression using flow cytometry...
March 21, 2017: Human Immunology
https://www.readbyqxmd.com/read/28319049/resisting-fatal-attraction-a-glioma-oncometabolite-prevents-cd8-t-cell-recruitment
#3
Liliana E Lucca, David A Hafler
Immunotherapy has emerged as a potent approach for treating aggressive cancers, such as non-small-cell lung tumors and metastatic melanoma. Clinical trials are now in progress for patients with malignant gliomas; however, a better understanding of how these tumors escape immune surveillance is required to enhance antitumor immune responses. With gliomas, the recruitment of CD8+ T cells to the tumor is impaired, in part preventing containment or elimination of the tumor. In this issue of the JCI, Kohanbash and colleagues present an elegant dissection of how gliomas exploit an enzymatic activity acquired through a common mutation to abrogate the migration of CD8+ T cells to the tumor...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28319047/isocitrate-dehydrogenase-mutations-suppress-stat1-and-cd8-t-cell-accumulation-in-gliomas
#4
Gary Kohanbash, Diego A Carrera, Shruti Shrivastav, Brian J Ahn, Naznin Jahan, Tali Mazor, Zinal S Chheda, Kira M Downey, Payal B Watchmaker, Casey Beppler, Rolf Warta, Nduka A Amankulor, Christel Herold-Mende, Joseph F Costello, Hideho Okada
Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are among the first genetic alterations observed during the development of lower-grade glioma (LGG). LGG-associated IDH mutations confer gain-of-function activity by converting α-ketoglutarate to the oncometabolite R-2-hydroxyglutarate (2HG). Clinical samples and gene expression data from The Cancer Genome Atlas (TCGA) demonstrate reduced expression of cytotoxic T lymphocyte-associated genes and IFN-γ-inducible chemokines, including CXCL10, in IDH-mutated (IDH-MUT) tumors compared with IDH-WT tumors...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28318762/gene-expression-profiling-reveals-genes-and-transcription-factors-associated-with-dilated-and-ischemic-cardiomyopathies
#5
Aiqing Qiao, Zhenying Zhao, Hui Zhang, Zhenyu Sun, Xiao Cui
AIMS: Dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) can cause heart failure, and this study aims to identify genes and transcription factors (TFs) associated with DCM and ICM. METHODS: Gene expression dataset GSE42955 was generated from GEO database, and it contained 12 DCM, 12 ICM, and 5 control samples. Differentially expressed genes (DEGs) were identified between DCM (or ICM) and controls. Gene functions were investigated, and their associations were analyzed using Enrichmentmap plugin in Cytoscape...
December 29, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28318643/cxcl10-alters-the-tumour-immune-microenvironment-and-disease-progression-in-a-syngeneic-murine-model-of-high-grade-serous-ovarian-cancer
#6
Katrina K Au, Nichole Peterson, Peter Truesdell, Gillian Reid-Schachter, Kasra Khalaj, Runhan Ren, Julie-Ann Francis, Charles H Graham, Andrew W Craig, Madhuri Koti
OBJECTIVE: We recently established that high STAT1 expression and associated T helper type I tumour immune microenvironment (TME) are prognostic and chemotherapy response predictive biomarkers in high-grade serous ovarian cancer (HGSC). STAT1 induced chemokine CXCL10 is key to the recruitment of lymphocytes in the TME and is significantly highly expressed in the tumours from patients with longer survival. In the current study we therefore aimed to elucidate the role CXCL10 in disease progression and tumour immune transcriptomic alterations using the ID8 syngeneic murine model of HGSC...
March 16, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28318085/inflammatory-double-hit-model-of-temporomandibular-joint-disorder-with-elevated-ccl2-cxcl9-cxcl10-rantes-and-behavioural-hypersensitivity-in-tnfr1-r2-mice
#7
S L McIlwrath, R Nesemeier, F Ma, H S Oz, L Zhang, K N Westlund
BACKGROUND: Patients with temporomandibular joint disorders (TMD), reactive arthritis and rheumatoid arthritis often have combined etiology of hereditary and microenvironmental factors contributing to joint pain. Multiple clinical and animal studies indicate 'double-hit' inflammatory insults can cause chronic inflammation. The first inflammatory insult primes the immune system and subsequent insults elicit amplified responses. The present 'double hit' study produced a chronic orofacial pain model in mice with genetic deletion of both TNFα receptors (TNFR1/R2-/-), investigating the main nociceptive signalling pathways in comparisons to wild type mice...
March 20, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28316371/znf395-is-an-activator-of-a-subset-of-ifn-stimulated-genes
#8
Linda Schroeder, Christine Herwartz, Darko Jordanovski, Gertrud Steger
Activation of the interferon (IFN) pathway in response to infection with pathogens results in the induction of IFN-stimulated genes (ISGs) including proinflammatory cytokines, which mount the proper antiviral immune response. However, aberrant expression of these genes is pathogenic to the host. In addition to IFN-induced transcription factors non-IFN-regulated factors contribute to the transcriptional control of ISGs. Here, we show by genome wide expression analysis, siRNA-mediated suppression and Doxycycline-induced overexpression that the cellular transcription factor ZNF395 activates a subset of ISGs including the chemokines CXCL10 and CXCL11 in keratinocytes...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28302565/inhibition-of-prmt5-suppresses-osteoclast-differentiation-and-partially-protects-against-ovariectomy-induced-bone-loss-through-downregulation-of-cxcl10-and-rsad2
#9
Yonghui Dong, Chao Song, Yuting Wang, Zuowei Lei, Fei Xu, Hanfeng Guan, Anmin Chen, Feng Li
Protein arginine methyltransferase 5 (PRMT5) is an arginine methylation methyltransferase that regulates various physiological processes. Abnormal PRMT5 activity has been reported in inflammation and various types of cancers. Because osteoclast differentiation is characterized by the activation of inflammation-related pathways, we speculated that PRMT5 may play a role in this process. In the present study, we found that PRMT5 was upregulated during osteoclast differentiation. Knockdown of PRMT5 with siRNA in bone marrow mononuclear cells (BMMs) resulted in inhibition of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation...
March 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28288328/case-control-exploratory-study-of-cerebrospinal-fluid-chemokines-cytokines-and-lymphocyte-subsets-in-childhood-tourette-syndrome-with-positive-streptococcal-markers
#10
Michael R Pranzatelli, Elizabeth D Tate, Tyler J Allison
A longstanding question is whether neuroinflammation is present in children symptomatic for Tourette syndrome (TS) with positive streptococcal serology and throat cultures. The objective was to directly test for it using modern hypothesis-driven approaches. Profiling studies for 14 immune cell types (flow cytometry), 7 chemokines/cytokines (ELISA), oligoclonal bands, and other immunoglobulins were performed in this IRB-approved study of 5 children with TS and streptococcal markers compared to data from 26 non-inflammatory pediatric neurological controls...
March 10, 2017: Cytokine
https://www.readbyqxmd.com/read/28284222/teriflunomide-and-monomethylfumarate-target-hiv-induced-neuroinflammation-and-neurotoxicity
#11
Björn Ambrosius, Simon Faissner, Kirsten Guse, Marec von Lehe, Thomas Grunwald, Ralf Gold, Bastian Grewe, Andrew Chan
HIV-associated neurocognitive disorders (HAND) affect about 50% of infected patients despite combined antiretroviral therapy (cART). Ongoing compartmentalized inflammation mediated by microglia which are activated by HIV-infected monocytes has been postulated to contribute to neurotoxicity independent from viral replication. Here, we investigated effects of teriflunomide and monomethylfumarate on monocyte/microglial activation and neurotoxicity. Human monocytoid cells (U937) transduced with a minimal HIV-Vector were co-cultured with human microglial cells (HMC3)...
March 11, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28283576/glucocorticoid-and-cytokine-crosstalk-feedback-feedforward-and-co-regulatory-interactions-determine-repression-or-resistance
#12
Robert Newton, Suharsh V Shah, Mohammed O Altonsy, Anthony N Gerber
Inflammatory signals induce complex feedback and feedforward systems that allow tight temporal control. Whereas glucocorticoids generally repress inflammatory gene expression, GR recruitment increases expression of negative feedback and feedforward regulators, including DUSP1, IRAK3, NFKBIA, TNFAIP3 or ZFP36. Moreover, GR cooperativity with factors, such as NF-κB, can enhance regulator expression to promote repression. Conversely, MAPKs, which are inhibited by glucocorticoids, limit expression of the transcription factor IRF1, and the host defense gene, CXCL10, through a feedforward control mechanism...
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28282579/interleukin-23-mediates-the-pathogenesis-of-lps-galn-induced-liver-injury-in-mice
#13
Suxia Bao, Qiang Zhao, Jianming Zheng, Ning Li, Chong Huang, Mingquan Chen, Qi Cheng, Mengqi Zhu, Kangkang Yu, Chenghai Liu, Guangfeng Shi
BACKGROUND: Interleukin-23 (IL-23) is required for T helper 17 (Th17) cell responses and IL-17 production in hepatitis B virus infection. A previous study showed that the IL-23/IL-17 axis aggravates immune injury in patients with chronic hepatitis B virus infection. However, the role of IL-23 in acute liver injury remains unclear. OBJECTIVE: The purpose of this study was to determine the role of the inflammatory cytokine IL-23 in lipopolysaccharide/d-galactosamine (LPS/GalN)-induced acute liver injury in mice...
March 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28282568/cxcl9-compensates-for-the-absence-of-cxcl10-during-recurrent-herpetic-stromal-keratitis
#14
Deena Tajfirouz, Devin M West, Xiao-Tang Yin, Chloe A Potter, Robyn Klein, Patrick M Stuart
Herpetic stromal keratitis (HSK) is a disease that is typically associated with reactivation of a latent HSV-1 infection. This disease is driven, in part, by chemokines that recruit leukocytes to the cornea. Surprisingly, neutralization of CXCL10 significantly reduced disease, while B6-CXCL10-/- mice exhibited worse disease compared with similarly infected wild-type controls. We hypothesized that compensatory up-regulation of CXCL9 occurs in the absence of CXCL10. Analysis of CXCL9 expression in HSV-1-infected B6 mice and B6-CXCL10-/- mice revealed significantly more CXCL9 in B6-XCL10-/- mice...
March 7, 2017: Virology
https://www.readbyqxmd.com/read/28279502/circulating-microparticle-subpopulations-in-systemic-lupus-erythematosus-are-affected-by-disease-activity
#15
Patricia López, Javier Rodríguez-Carrio, Aleida Martínez-Zapico, Luis Caminal-Montero, Ana Suárez
BACKGROUND: Immune cells under chronic inflammation shed microparticles (MPs) that could fuel the inflammatory responses and atherosclerosis typically presented in systemic lupus erythematosus (SLE). This study analyzes total and subset-specific MPs from SLE patients and their possible influence on clinical features, leukocyte activation and serum cytokines. METHODS: Total MPs and those derived from platelets, endothelial cells, monocytes, granulocytes and T-cells were quantified in plasma of 106 SLE patients and 33 healthy controls by flow cytometry...
March 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28278706/high-expression-levels-of-ip10-cxcl10-are-associated-with-modulation-of-the-natural-killer-cell-compartment-in-multiple-myeloma
#16
Giovanni Bernardini, Elisabetta Vulpis, Valentina Bonanni, Helena Stabile, Maria Rosaria Ricciardi, Maria Teresa Petrucci, Angela Gismondi, Angela Santoni, Alessandra Zingoni
No abstract text is available yet for this article.
February 28, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28275176/human-bronchial-epithelium-orchestrates-dendritic-cell-activation-in-severe-asthma
#17
Delphine Gras, Asuncion Martinez-Anton, Arnaud Bourdin, Celine Garulli, Laure de Senneville, Isabelle Vachier, Joana Vitte, Pascal Chanez
The innate immune response is impaired in asthma, with increased epithelial release of C-X-C motif chemokine ligand (CXCL)8, interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP). We hypothesised that dendritic cells might modulate the hyperresponsive epithelium in severe asthma.For this purpose, we investigated epithelial-dendritic crosstalk in normal and diseased conditions, and because ultrafine particulate matter may affect asthmatic airways, we investigated its impact on this crosstalk. Air-liquid interface cultures of human bronchial epithelial cells (HBEC) of control subjects (cHBEC) or severe asthma patients (saHBEC) were co-cultured with monocyte-derived dendritic cells (moDC)...
March 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28270451/validation-of-single-nucleotide-polymorphisms-in-invasive-aspergillosis-following-hematopoietic-cell-transplantation
#18
Cynthia E Fisher, Tobias M Hohl, Wenhong Fan, Barry E Storer, David M Levine, Lu Ping Zhao, Paul J Martin, Edus H Warren, Michael Boeckh, John A Hansen
Invasive aspergillosis (IA) is a significant cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Previous studies have reported an association between IA development and single nucleotide polymorphisms (SNPs), but many have not been replicated in a separate cohort. The presence of a positive serum galactomannan assay (SGM+) has also been associated with a worse prognosis in patients with IA, and genetic determinants in this subset of patients have not been systematically studied...
March 7, 2017: Blood
https://www.readbyqxmd.com/read/28265273/new-data-on-human-macrophages-polarization-by-hymenolepis-diminuta-tapeworm-an-in-vitro-study
#19
Anna Zawistowska-Deniziak, Katarzyna Basałaj, Barbara Strojny, Daniel Młocicki
Helminths and their products can suppress the host immune response to escape host defense mechanisms and establish chronic infections. Current studies indicate that macrophages play a key role in the immune response to pathogen invasion. They can be polarized into two distinct phenotypes: M1 and M2. The present paper examines the impact of the adult Hymenolepis diminuta (HD) tapeworm and its excretory/secretory products (ESP) on THP-1 macrophages. Monocytes were differentiated into macrophages and cultured with a living parasite or its ESP...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28262979/mixed-lineage-kinase-3-mediates-the-induction-of-cxcl10-by-a-stat1-dependent-mechanism-during-hepatocyte-lipotoxicity
#20
Kyoko Tomita, Ayano Niibe, Brittany L Freeman, Steven F Bronk, Petra Hirsova, Samar H Ibrahim
BACKGROUND AND AIMS: Saturated free fatty acids (SFA) and their toxic metabolites contribute to hepatocyte lipotoxicity in nonalcoholic steatohepatitis (NASH). We previously reported that hepatocytes, under lipotoxic stress, express the potent macrophage chemotactic ligand C-X-C motif chemokine 10 (CXCL10) and release CXCL10-enriched extracellular vesicles by a mixed lineage kinase (MLK) 3-dependent mechanism. In the current study, we sought to examine the signaling pathway responsible for CXCL10 induction during hepatocyte lipotoxicity...
March 6, 2017: Journal of Cellular Biochemistry
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