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Cytokine signal transduction

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https://www.readbyqxmd.com/read/28344808/safety-tumor-trafficking-and-immunogenicity-of-chimeric-antigen-receptor-car-t-cells-specific-for-tag-72-in-colorectal-cancer
#1
Kristen M Hege, Emily K Bergsland, George A Fisher, John J Nemunaitis, Robert S Warren, James G McArthur, Andy A Lin, Jeffrey Schlom, Carl H June, Stephen A Sherwin
BACKGROUND: T cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s. METHODS: Patients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28343998/carnosic-acid-ca-attenuates-collagen-induced-arthritis-in-db-db-mice-via-inflammation-suppression-by-regulating-ros-dependent-p38-pathway
#2
Guangtao Xia, Xia Wang, Hongsheng Sun, Yuhong Qin, Min Fu
Rheumatoid arthritis (RA) is a multifactorial autoimmune disease, characterized by inflammation of synovial joints. Carnosic acid (CA) is a phenolic diterpene isolated from Rosmarinus officinails, playing a central role in cytoprotective responses to oxidative stress and inflammation response. Our study aimed to investigate the effects of CA on RA progression in diabetic animals. Carnosic acid (CA) was used to treat collagen-induced arthritis (CIA)-induced db/db mice. Blood glucose, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were investigated to explore insulin resistance...
March 23, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28342757/role-of-enzymatic-free-radical-scavengers-in-management-of-oxidative-stress-and-autoimmune-disorders
#3
REVIEW
Shikha Srivastava, Deependra Singh, Satish Patel, Manju R Singh
Autoimmune disorders are distinct with over production and accumulation of free radicals due to its undisclosed genesis. The cause of numerous disorders as cancer, arthritis, psoriasis, diabetes, alzheimer's, cardiovascular disease, Parkinson's, respiratory distress syndrome, colitis, crohn's, pulmonary fibrosis, obesity and ageing have been associated with immune dysfunction and oxidative stress. In an oxidative stress, reactive oxygen species generally provoke the series of oxidation at cellular level. The buildup of free radicals in turn triggers various inflammatory cells causing release of various inflammatory interleukins, cytokines, chemokines, and tumor necrosis factors which mediate signal transduction and transcription pathways as nuclear factor- kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), hypoxia-inducible factor-1 (HIF-1α) and nuclear factor-erythroid 2-related factor (Nrf2)...
March 22, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28337297/protective-effect-of-a-novel-antibody-against-tlr2-on-zymosan-induced-acute-peritonitis-in-nf-%C3%AE%C2%BAb-transgenic-mice
#4
Qingjun Pan, Jun Cai, Yanxia Peng, Haiyan Xiao, Lifang Zhang, Jinying Chen, Huafeng Liu
In addition to antibiotic therapy for treatment of peritonitis, biologics have also been found to exhibit both anti-inflammatory and inflammation-resolving properties. Here, we first developed NF-κB transgenic mice with zymosan-induced acute peritonitis to investigate the effects of a novel anti-Toll-like receptor (TLR)2 antibody (anti-T20). In this mouse model, anti-T20 treatment significantly attenuated the increase of peritoneal NF-κB activity and serum levels of inflammatory cytokines, including monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6 and tumor necrosis factor (TNF)-α, in a dose-dependent manner compared to mice treated with isotype control antibody...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28326484/genome-wide-transcriptional-analysis-of-cardiovascular-related-genes-and-pathways-induced-by-pm2-5-in-human-myocardial-cells
#5
Lin Feng, Xiaozhe Yang, Collins Otieno Asweto, Jing Wu, Yannan Zhang, Hejing Hu, Yanfeng Shi, Junchao Duan, Zhiwei Sun
Air pollution has been a major environment-related health threat. Most of the studies on PM2.5 toxicity have verified on the cardiovascular system and endothelial cells. However, researches on PM2.5-induced myocardial-related toxicity are limited. This study aims to fully understand the toxic effects of PM2.5 on human myocardial cell (AC16) and explore its molecular mechanism based on microarray analysis and bioinformatics analysis. Microarray data analysis manifested that PM2.5-induced toxicity affected expression of 472 genes compared with the control group, including 166 upregulated genes and 306 downregulated genes in human myocardial (AC16) cells...
March 22, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28316063/endothelial-long-non-coding-rnas-regulated-by-oxidized-ldl
#6
Krishna K Singh, Pratiek N Matkar, Yi Pan, Adrian Quan, Vijay Gupta, Hwee Teoh, Mohammed Al-Omran, Subodh Verma
Oxidized low-density lipoprotein (oxLDL) plays a central role in the pathogenesis of atherosclerosis, in part via an effect to promote endothelial dysfunction. In the present study, we evaluated the expression profiles of long non-coding RNAs (lncRNAs) and protein-coding mRNAs in endothelial cells following oxLDL stimulation. LncRNAs and mRNAs from human umbilical vein endothelial cells (HUVECs) were profiled with the Arraystar Human lncRNA Expression Microarray V3.0 following 24 h of oxLDL treatment (100 µg/mL)...
March 18, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28315704/interleukin-6-and-prostate-cancer-current-developments-and-unsolved-questions
#7
Zoran Culig, Martin Puhr
Interleukin (IL)-6 is a pro-inflammatory cytokine that is expressed in prostate tumors and in the stromal tumor micro-enviroment. It is known to regulate proliferation, apoptosis, angiogenesis, and differentiation. The signaling pathway of Janus kinase and signal transducer and activator of transcription (STAT)3, which is activated by IL-6, is in the focus of scientific investigations for improved treatment approaches. Different effects of IL-6 and/or STAT3 on tumor cell growth have been observed in human and murine prostate cancer (PCa) models...
March 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28303575/isoform-localization-of-dectin-1-regulates-the-signaling-quality-of-anti-fungal-immunity
#8
Mike Fischer, Jörg P Müller, Bärbel Spies-Weisshart, Christine Gräfe, Oliver Kurzai, Kerstin Hünniger, Andreas Hochhaus, Sebastian Scholl, Ulf Schnetzke
Dectin-1 is recognized as a major receptor for fungal ß-glucans and contributes to anti-fungal immunity. Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site. Here, we analyzed the expression of both isoforms in human monocyte-derived cells. The cellular localization on cell lines stably expressing either Dectin-1 isoform A or B was studied by flow cytometry and confocal laser scanning microscopy. Intracellular protein signaling and cytokine production was analyzed by immunoblotting and cytometric bead arrays, respectively...
March 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28290727/the-toxic-effects-of-benzo-a-pyrene-on-activated-mouse-t-cells-in-vitro
#9
Shuang Guan, Yixuan Huang, Zhe Feng, Linli Xu, Yingli Jin, Jing Lu
Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon contaminant that is widely present in environmental sources, including food. This study aims to clarify the effects of B[a]P toxicity on activated mouse T cells in vitro. Our results show that B[a]P markedly inhibited Concanavalin A (ConA)-induced T lymphocyte proliferation and suppressed the production of the cytokines Interferon (IFN)-γ, Interleukin (IL)-2 and IL-4. Western blot and protein-DNA interaction assays were used to study how B[a]P affects signal transduction...
March 14, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28259699/chicken-il-26-regulates-immune-responses-through-the-jak-stat-and-nf-%C3%AE%C2%BAb-signaling-pathways
#10
Anh Duc Truong, Yeojin Hong, Cong Thanh Hoang, Janggeun Lee, Yeong Ho Hong
Chicken interleukin 26 (ChIL-26), a member of the IL-10 family, is expressed in T cells and can induce expression of proinflammatory cytokines. We examined the response of signal transduction pathways to ChIL-26 stimulation in the chicken T (CU91), macrophage (HD11), and fibroblast (OU2) cell lines. ChIL-26 activated JAK2 and TYK2 phosphorylation, as well as activation of STAT1, STAT3, and SHP2 via tyrosine/serine residues. We also showed that ChIL-26 activates the phosphorylation of NF-κB1, TAK1, and MyD88 kinase, which are key regulators of NF-κB signaling pathways...
March 2, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28255960/jak-stat-signaling-as-a-target-for-inflammatory-and-autoimmune-diseases-current-and-future-prospects
#11
REVIEW
Shubhasree Banerjee, Ann Biehl, Massimo Gadina, Sarfaraz Hasni, Daniella M Schwartz
The Janus kinase/signal transduction and activator of transcription (JAK-STAT) signaling pathway is implicated in the pathogenesis of inflammatory and autoimmune diseases including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Many cytokines involved in the pathogenesis of autoimmune and inflammatory diseases use JAKs and STATs to transduce intracellular signals. Mutations in JAK and STAT genes cause a number of immunodeficiency syndromes, and polymorphisms in these genes are associated with autoimmune diseases...
March 3, 2017: Drugs
https://www.readbyqxmd.com/read/28254169/il-17-signaling-the-yin-and-the-yang
#12
REVIEW
Nilesh Amatya, Abhishek V Garg, Sarah L Gaffen
Interleukin (IL)-17 is the founding member of a novel family of inflammatory cytokines. While the proinflammatory properties of IL-17 are key to its host-protective capacity, unrestrained IL-17 signaling is associated with immunopathology, autoimmune disease, and cancer progression. In this review we discuss both the activators and the inhibitors of IL-17 signal transduction, and also the physiological implications of these events. We highlight the surprisingly diverse means by which these regulators control expression of IL-17-dependent inflammatory genes, as well as the major target cells that respond to IL-17 signaling...
February 18, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28245601/distinct-antigen-delivery-systems-induce-dendritic-cells-divergent-transcriptional-response-new-insights-from-a-comparative-and-reproducible-computational-analysis
#13
Valerio Costa, Dario Righelli, Francesco Russo, Piergiuseppe De Berardinis, Claudia Angelini, Luciana D'Apice
Vaccination is the most successful and cost-effective method to prevent infectious diseases. However, many vaccine antigens have poor in vivo immunogenic potential and need adjuvants to enhance immune response. The application of systems biology to immunity and vaccinology has yielded crucial insights about how vaccines and adjuvants work. We have previously characterized two safe and powerful delivery systems derived from non-pathogenic prokaryotic organisms: E2 and fd filamentous bacteriophage systems. They elicit an in vivo immune response inducing CD8+ T-cell responses, even in absence of adjuvants or stimuli for dendritic cells' maturation...
February 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28245561/negative-regulators-of-jak-stat-signaling-in-rheumatoid-arthritis-and-osteoarthritis
#14
REVIEW
Charles J Malemud
Elevated levels of pro-inflammatory cytokines are generally thought to be responsible for driving the progression of synovial joint inflammation in rheumatoid arthritis (RA) and osteoarthritis (OA). These cytokines activate several signal transduction pathways, including the Janus kinase/Signal Transducers and Activators of Transcription (JAK/STAT), Stress-Activated/Mitogen-Activated Protein Kinase (SAPK/MAPK) and phosphatidylinositol-3-kinase/Akt/mechanistic target of rapamycin (PI3K/Akt/mTOR) pathways which regulate numerous cellular responses...
February 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28245546/luteolin-inhibits-fibrillary-%C3%AE-amyloid1-40-induced-inflammation-in-a-human-blood-brain-barrier-model-by-suppressing-the-p38-mapk-mediated-nf-%C3%AE%C2%BAb-signaling-pathways
#15
Jun-Xia Zhang, Jian-Guo Xing, Lin-Lin Wang, Hai-Lun Jiang, Shui-Long Guo, Rui Liu
Amyloid-β peptides (Aβ) exist in several forms and are known as key modulators of Alzheimer's disease (AD). Fibrillary Aβ (fAβ) has been found to disrupt the blood-brain barrier (BBB) by triggering and promoting inflammation. In this study, luteolin, a naturally occurring flavonoid that has shown beneficial properties in the central nervous system, was evaluated as a potential agent to preserve barrier function and inhibit inflammatory responses at the BBB that was injured by fAβ1-40. We established an in vitro BBB model by co-culturing human brain microvascular endothelial cells (hBMECs) and human astrocytes (hAs) under fAβ1-40-damaged conditions and investigated the effect of luteolin by analyzing cellular toxicity, barrier function, cytokine production and inflammation-related intracellular signaling pathways...
February 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28243252/neurobiological-mechanism-of-acupuncture-for-relieving-visceral-pain-of-gastrointestinal-origin
#16
REVIEW
Fang Zhang, Luyi Wu, Jimeng Zhao, Tingting Lv, Zhihai Hu, Zhijun Weng, Shuoshuo Wang, Huangan Wu, Huirong Liu
It is currently accepted that the neural transduction pathways of gastrointestinal (GI) visceral pain include the peripheral and central pathways. Existing research on the neurological mechanism of electroacupuncture (EA) in the treatment of GI visceral pain has primarily been concerned with the regulation of relevant transduction pathways. The generation of pain involves a series of processes, including energy transduction of stimulatory signals in the sensory nerve endings (signal transduction), subsequent conduction in primary afferent nerve fibers of dorsal root ganglia, and transmission to spinal dorsal horn neurons, the ascending transmission of sensory signals in the central nervous system, and the processing of sensory signals in the cerebral cortex...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28242024/enhancement-of-macrophage-inflammatory-responses-by-ccl2-is-correlated-with-increased-mir-9-expression-and-downregulation-of-the-erk1-2-phosphatase-dusp6
#17
William F Carson, Sarah E Salter-Green, Melissa M Scola, Amrita Joshi, Katherine A Gallagher, Steven L Kunkel
Macrophage polarization plays a central role in both protective immunity and immunopathology. While the role of cytokines in driving macrophage polarization is well characterized, less is understood about the role of chemokines. The purpose of this study was to determine if CC chemokine 2 (CCL2/MCP1) could influence macrophage polarization in response to subsequent activation with cytokines and microbial products. Treatment of bone marrow-derived macrophages with CCL2 alone did not result in increased expression of either classical or alternatively-activated macrophage genes as compared to standard skewing cytokines or Toll-like receptor agonists...
February 22, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28241443/emerging-cytokine-biosensors-with-optical-detection-modalities-and-nanomaterial-enabled-signal-enhancement
#18
REVIEW
Manpreet Singh, Johnson Truong, W Brian Reeves, Jong-In Hahm
Protein biomarkers, especially cytokines, play a pivotal role in the diagnosis and treatment of a wide spectrum of diseases. Therefore, a critical need for advanced cytokine sensors has been rapidly growing and will continue to expand to promote clinical testing, new biomarker development, and disease studies. In particular, sensors employing transduction principles of various optical modalities have emerged as the most common means of detection. In typical cytokine assays which are based on the binding affinities between the analytes of cytokines and their specific antibodies, optical schemes represent the most widely used mechanisms, with some serving as the gold standard against which all existing and new sensors are benchmarked...
February 22, 2017: Sensors
https://www.readbyqxmd.com/read/28235408/the-chinese-prescription-lianhuaqingwen-capsule-exerts-anti-influenza-activity-through-the-inhibition-of-viral-propagation-and-impacts-immune-function
#19
Yuewen Ding, Lijuan Zeng, Runfeng Li, Qiaoyan Chen, Beixian Zhou, Qiaolian Chen, Pui Leng Cheng, Wang Yutao, Jingping Zheng, Zifeng Yang, Fengxue Zhang
BACKGROUND: Lianhuaqingwen Capsule (LH-C) is a traditional Chinese medicine (TCM) formula used to treat respiratory tract infectious diseases in Chinese. The aim of this study was to determine the antiviral activity of LH-C and its immunomodulatory effects on viral infection. METHOD: The in vitro cytotoxicity and antiviral activity of LH-C was determined by MTT and Plaque reduction assays. Time course study under single-cycle virus growth conditions were used to determine which stage of viral replication was blocked...
February 24, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28222623/interferon-%C3%AE-induced-cd100-on-na%C3%A3-ve-cd8-t-cells-enhances-antiviral-responses-to-hepatitis-c-infection-through-cd72-signal-transduction
#20
Bing Jie Li, Yu He, Ying Zhang, Yong Hong Guo, Yun Zhou, Pei Xin Zhang, Wei Wang, Jie Ru Zhao, Jin Ge Li, Wei Ze Zuo, Chao Fan, Zhan Sheng Jia
Objectives We investigated the effects of CD100 on naïve CD8(+) T cells during hepatitis C virus (HCV) infection after interferon-α (IFN-α) therapy to clarify the mechanism underlying the effect of IFN-α in enhancing the antiviral response. Methods The CD100 molecules on subsets of CD8(+) T cells were analysed with flow cytometry. The effects of CD100-overexpressing naïve CD8(+) T cells were determined with ELISAs and an MTT cytotoxicity assay. The role of CD100-CD72 signal transduction was analysed with a neutralization and transwell assays...
February 2017: Journal of International Medical Research
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