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Cytokine signaling

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https://www.readbyqxmd.com/read/28346521/hiv-1-gp120-envelope-glycoprotein-determinants-for-cytokine-burst-in-human-monocytes
#1
Benoît Levast, Lucie Barblu, Mathieu Coutu, Jérémie Prévost, Nathalie Brassard, Adam Peres, Camille Stegen, Joaquín Madrenas, Daniel E Kaufmann, Andrés Finzi
The first step of HIV infection involves the interaction of the gp120 envelope glycoprotein to its receptor CD4, mainly expressed on CD4+ T cells. Besides its role on HIV-1 entry, the gp120 has been shown to be involved in the production of IL-1, IL-6, CCL20 and other innate response cytokines by bystander, uninfected CD4+ T cells and monocytes. However, the gp120 determinants involved in these functions are not completely understood. Whether signalling leading to cytokine production is due to CD4 or other receptors is still unclear...
2017: PloS One
https://www.readbyqxmd.com/read/28346354/anti-inflammatory-properties-of-irisin-mediator-of-physical-activity-are-connected-with-tlr4-myd88-signaling-pathway-activation
#2
Agnieszka Irena Mazur-Bialy, Ewa Pocheć, Marcin Zarawski
Irisin, an adipomiokine known as a mediator of physical activity, induces the browning of adipose tissue and it has potentially protective properties in the development of obesity-related states, such as insulin resistance, arteriosclerosis, and type 2 diabetes. Despite numerous studies conducted on this factor, still little is known about its impact on the functioning of immunocompetent cells, but its potential anti-inflammatory properties were previously suggested. In the current study we investigated the role of irisin (0-100 nM) in the downstream pathway activation of Toll-like receptor 4 (TLR4) in RAW 264...
March 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28346226/a-tlr9-dependent-checkpoint-governs-b-cell-responses-to-dna-containing-antigens
#3
Vishal J Sindhava, Michael A Oropallo, Krishna Moody, Martin Naradikian, Lauren E Higdon, Lin Zhou, Arpita Myles, Nathaniel Green, Kerstin Nündel, William Stohl, Amanda M Schmidt, Wei Cao, Stephanie Dorta-Estremera, Taku Kambayashi, Ann Marshak-Rothstein, Michael P Cancro
Mature B cell pools retain a substantial proportion of polyreactive and self-reactive clonotypes, suggesting that activation checkpoints exist to reduce the initiation of autoreactive B cell responses. Here, we have described a relationship among the B cell receptor (BCR), TLR9, and cytokine signals that regulate B cell responses to DNA-containing antigens. In both mouse and human B cells, BCR ligands that deliver a TLR9 agonist induce an initial proliferative burst that is followed by apoptotic death. The latter mechanism involves p38-dependent G1 cell-cycle arrest and subsequent intrinsic mitochondrial apoptosis and is shared by all preimmune murine B cell subsets and CD27- human B cells...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28346012/lymphangiogenesis-fuel-smoke-or-extinguisher-of-inflammation-s-fire
#4
Gabriella R Abouelkheir, Bradley D Upchurch, Joseph M Rutkowski
Lymphangiogenesis is a recognized hallmark of inflammatory processes in tissues and organs as diverse as the skin, heart, bowel, and airways. In clinical and animal models wherein the signaling processes of lymphangiogenesis are manipulated, most studies demonstrate that an expanded lymphatic vasculature is necessary for the resolution of inflammation. The fundamental roles that lymphatics play in fluid clearance and immune cell trafficking from the periphery make these results seemingly obvious as a mechanism of alleviating locally inflamed environments: the lymphatics are simply providing a drain...
April 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28345602/a-primary-human-macrophage-enteroid-co-culture-model-to-investigate-mucosal-gut-physiology-and-host-pathogen-interactions
#5
Gaelle Noel, Nicholas W Baetz, Janet F Staab, Mark Donowitz, Olga Kovbasnjuk, Marcela F Pasetti, Nicholas C Zachos
Integration of the intestinal epithelium and the mucosal immune system is critical for gut homeostasis. The intestinal epithelium is a functional barrier that secludes luminal content, senses changes in the gut microenvironment, and releases immune regulators that signal underlying immune cells. However, interactions between epithelial and innate immune cells to maintain barrier integrity and prevent infection are complex and poorly understood. We developed and characterized a primary human macrophage-enteroid co-culture model for in-depth studies of epithelial and macrophage interactions...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345549/sub-anesthesia-dose-of-isoflurane-in-60-oxygen-reduces-inflammatory-responses-in-experimental-sepsis-models
#6
Yi Huang, Xiao-Xia Wang, Dong-Dong Sun, Ze-Xin Zhang, Wan-Wan Yang, Tian Shao, Han Han, Er-Fei Zhang, Zhong-Shu Pu, Zuo-Xu Hou, Hai-Long Dong, Li-Ze Xiong, Li-Chao Hou
BACKGROUND: Sepsis is a major cause of mortality in Intensive Care Units. Anesthetic dose isoflurane and 100% oxygen were proved to be beneficial in sepsis; however, their application in septic patients is limited because long-term hyperoxia may induce oxygen toxicity and anesthetic dose isoflurane has potential adverse consequences. This study was scheduled to find the optimal combination of isoflurane and oxygen in protecting experimental sepsis and its mechanisms. METHODS: The effects of combined therapy with isoflurane and oxygen on lung injury and sepsis were determined in animal models of sepsis induced by cecal ligation and puncture (CLP) or intraperitoneal injection of lipopolysaccharide (LPS) or zymosan...
April 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28345393/inhibitory-effects-of-3%C3%AE-hydroxy-lup-20-29-en-23-28-dioic-acid-on-lipopolysaccharide-induced-tnf-%C3%AE-il-1%C3%AE-and-the-high-mobility-group-box-1-release-in-macrophages
#7
Xiang-Qian Liu, Qin-Peng Zou, Jian-Jun Huang, Chang-Soo Yook, Wan-Kyunn Whang, Hyeong-Kyu Lee, Ok-Kyoung Kwon
We investigated the anti-inflammatory effects of 3α-hydroxy-lup-20(29)-en-23, 28-dioic acid (HLEDA)-a lupane-type triterpene isolated from leaves of Acanthopanax gracilistylus W. W.Smith (AGS), as well as the underlying molecular mechanisms in lipopolysaccharide (LPS)-induced RAW264.7 cells. Our results demonstrated that HLEDA concentration-dependently reduced the production of nitric oxide (NO), significantly suppressed LPS-induced expression of TNF-α and IL-1β at the mRNA and protein levels in RAW264...
March 27, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28345165/interleukin-1-inhibition-facilitates-recovery-from-liver-injury-and-promotes-regeneration-of-hepatocytes-in-alcoholic-hepatitis-in-mice
#8
Arvin Iracheta-Vellve, Jan Petrasek, Benedek Gyogyosi, Shashi Bala, Timea Csak, Karen Kodys, Gyongyi Szabo
BACKGROUND & AIMS: Inflammation and impaired hepatocyte regeneration contribute to liver failure in alcoholic hepatitis (AH). Interleukin (IL)-1 is a key inflammatory cytokine in the pathobiology of AH. The role of IL-1 in liver regeneration in the recovery phase of alcohol-induced liver injury is unknown. METHODS: Here we tested IL-1 receptor antagonist to block IL-1 signaling in a mouse model of acute-on-chronic liver injury on liver inflammation and hepatocyte regeneration in AH...
March 26, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28344878/targeting-cytokine-signaling-checkpoint-cis-activates-nk-cells-to-protect-from-tumor-initiation-and-metastasis
#9
Eva M Putz, Camille Guillerey, Kevin Kos, Kimberley Stannard, Kim Miles, Rebecca B Delconte, Kazuyoshi Takeda, Sandra E Nicholson, Nicholas D Huntington, Mark J Smyth
The cytokine-induced SH2-containing protein CIS belongs to the suppressor of cytokine signaling (SOCS) protein family. Here, we show the critical role of CIS in suppressing natural killer (NK) cell control of tumor initiation and metastasis. Cish-deficient mice were highly resistant to methylcholanthrene-induced sarcoma formation and protected from lung metastasis of B16F10 melanoma and RM-1 prostate carcinoma cells. In contrast, the growth of primary subcutaneous tumors, including those expressing the foreign antigen OVA, was unchanged in Cish-deficient mice...
2017: Oncoimmunology
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
#10
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/28344752/involvement-of-cbl-b-mediated-macrophage-inactivation-in-insulin-resistance
#11
REVIEW
Tomoki Abe, Katsuya Hirasaka, Takeshi Nikawa
Aging and overnutrition cause obesity in rodents and humans. It is well-known that obesity causes various diseases by producing insulin resistance (IR). Macrophages infiltrate the adipose tissue (AT) of obese individuals and cause chronic low-level inflammation associated with IR. Macrophage infiltration is regulated by the chemokines that are released from hypertrophied adipocytes and the immune cells in AT. Saturated fatty acids are recognized by toll-like receptor 4 (TLR4) and induce inflammatory responses in AT macrophages (ATMs)...
March 15, 2017: World Journal of Diabetes
https://www.readbyqxmd.com/read/28344581/type-i-interferons-as-regulators-of-lung-inflammation
#12
REVIEW
Spyridon Makris, Michelle Paulsen, Cecilia Johansson
Immune responses to lung infections must be tightly regulated in order to permit pathogen eradication while maintaining organ function. Exuberant or dysregulated inflammation can impair gas exchange and underlies many instances of lung disease. An important driver of inflammation in the lung is the interferon (IFN) response. Type I IFNs are antiviral cytokines that induce a large range of proteins that impair viral replication in infected cells. This cell-intrinsic action plays a crucial role in protecting the lungs from spread of respiratory viruses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28344558/role-of-autonomic-nervous-system-and-orexinergic-system-on-adipose-tissue
#13
REVIEW
Giovanni Messina, Anna Valenzano, Fiorenzo Moscatelli, Monica Salerno, Antonio Lonigro, Teresa Esposito, Vincenzo Monda, Gaetano Corso, Antonietta Messina, Andrea Viggiano, Antonio I Triggiani, Sergio Chieffi, Giuseppe Guglielmi, Marcellino Monda, Giuseppe Cibelli
Adipose tissue, defined as white adipose tissue (WAT) and brown adipose tissue (BAT), is a biological caloric reservoir; in response to over-nutrition it expands and, in response to energy deficit, it releases lipids. The WAT primarily stores energy as triglycerides, whereas BAT dissipates chemical energy as heat. In mammals, the BAT is a key site for heat production and an attractive target to promote weight loss. The autonomic nervous system (ANS) exerts a direct control at the cellular and molecular levels in adiposity...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28344354/hdac1-3-inhibitor-ms-275-enhances-il10-expression-in-raw264-7-macrophages-and-reduces-cigarette-smoke-induced-airway-inflammation-in-mice
#14
Niek G J Leus, Thea van den Bosch, Petra E van der Wouden, Kim Krist, Maria E Ourailidou, Nikolaos Eleftheriadis, Loes E M Kistemaker, Sophie Bos, Rutger A F Gjaltema, Solomon A Mekonnen, Rainer Bischoff, Reinoud Gosens, Hidde J Haisma, Frank J Dekker
Chronic obstructive pulmonary disease (COPD) constitutes a major health burden. Studying underlying molecular mechanisms could lead to new therapeutic targets. Macrophages are orchestrators of COPD, by releasing pro-inflammatory cytokines. This process relies on transcription factors such as NF-κB, among others. NF-κB is regulated by lysine acetylation; a post-translational modification installed by histone acetyltransferases and removed by histone deacetylases (HDACs). We hypothesized that small molecule HDAC inhibitors (HDACi) targeting class I HDACs members that can regulate NF-κB could attenuate inflammatory responses in COPD via modulation of the NF-κB signaling output...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344207/dipeptidyl-peptidase-iv-inhibition-for-the-treatment-of-cardiovascular-disease%C3%A3-recent-insights-focusing-on-angiogenesis-and-neovascularization
#15
Yanna Lei, Lina Hu, Guang Yang, Limei Piao, Minggen Jin, Xianwu Cheng
Dipeptidyl peptidase IV (DPP-IV) is a complex enzyme that acts as a membrane-anchored cell surface exopeptidase and transmits intracellular signals through a small intracellular tail. DPP-IV exists in human blood in a soluble form, and truncates a large number of peptide hormones, chemokines, cytokines, and growth factors in vitro and in vivo. DPP-IV has gained considerable interest as a therapeutic target, and a variety of DPP-IV inhibitors that prolong the insulinotropic effects of glucagon-like peptide-1 (GLP-1) are widely used in clinical settings as antidiabetic drugs...
March 25, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
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
#16
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/28343791/androgen-receptor-deficient-islet-%C3%AE-cells-exhibit-alteration-in-genetic-markers-of-insulin-secretion-and-inflammation-a-transcriptome-analysis-in-the-male-mouse
#17
Weiwei Xu, Tianhua Niu, Beibei Xu, Guadalupe Navarro, Matthew J Schipma, Franck Mauvais-Jarvis
AIMS: Testosterone action is mediated via the androgen receptor (AR). We have reported that male mice lacking AR selectively in β-cells (βARKO(-/y)) develop decreased glucose-stimulated insulin secretion (GSIS), producing glucose intolerance. We showed that testosterone action on AR in β-cells amplifies the insulinotropic action of GLP-1 on its receptor via a cAMP-dependent protein kinase-A pathway. METHODS: To investigate AR-dependent gene networks in β-cells, we performed a high throughput whole transcriptome sequencing (RNA-Seq) in islets from male βARKO(-/y) and control mice...
March 9, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28343701/toll-like-receptor-8-agonist-nanoparticles-mimic-immunomodulating-effects-of-the-live-bcg-vaccine-and-enhance-neonatal-innate-and-adaptive-immune-responses
#18
David J Dowling, Evan A Scott, Annette Scheid, Ilana Bergelson, Sweta Joshi, Carlo Pietrasanta, Spencer Brightman, Guzman Sanchez-Schmitz, Simon D Van Haren, Jana Ninković, Dina Kats, Cristiana Guiducci, Alexandre de Titta, Daniel K Bonner, Sachiko Hirosue, Melody A Swartz, Jeffrey A Hubbell, Ofer Levy
BACKGROUND: Newborns display distinct immune responses, leaving them vulnerable to infections and impairing immunization. Targeting newborn dendritic cells (DCs), which integrate vaccine signals into adaptive immune responses, might enable development of age-specific vaccine formulations to overcome suboptimal immunization. OBJECTIVE: Small-molecule imidazoquinoline Toll-like receptor (TLR) 8 agonists robustly activate newborn DCs but can result in reactogenicity when delivered in soluble form...
March 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28343601/effects-of-rg7652-a-monoclonal-antibody-against-pcsk9-on-ldl-c-ldl-c-subfractions-and-inflammatory-biomarkers-in-patients-at-high-risk-of-or-with-established-coronary-heart-disease-from-the-phase-2-equator-study
#19
Amos Baruch, Sofia Mosesova, John D Davis, Nageshwar Budha, Alexandr Vilimovskij, Robert Kahn, Kun Peng, Kyra J Cowan, Laura Pascasio Harris, Thomas Gelzleichter, Josh Lehrer, John C Davis, Whittemore G Tingley
RG7652 (MPSK3169A), a fully human immunoglobulin G1 (IgG1) monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9 (PCSK9), blocks the interaction between PCSK9 and low-density lipoprotein (LDL) receptor. EQUATOR (ClinicalTrials.govNCT01609140), a randomized, double-blind, and dose-ranging phase 2 study, evaluated RG7652 in patients (1) at high risk for or (2) with coronary heart disease (CHD). The primary end point was change in LDL cholesterol (LDL-C) from baseline to day 169. Patients (n = 248; median age, 64 years; 57% men; 52% with established CHD; 82% on statins) with baseline LDL-C levels of 90 to 250 mg/dl (mean, 126 mg/dl) continuing on standard-of-care therapy were randomized to receive 1 of 5 RG7652 doses or placebo, subcutaneously every 4, 8, or 12 weeks for 24 weeks...
March 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28343272/effect-of-atra-and-ato-on-the-expression-of-tissue-factor-in-nb4-acute-promyelocytic-leukemia-cells-and-regulatory-function-of-the-inflammatory-cytokines-tnf-and-il-1%C3%AE
#20
Sylvie Dunoyer-Geindre, Anne-Sophie Rivier-Cordey, Olga Tsopra, Thomas Lecompte, Egbert K O Kruithof
The characteristic hemorrhages of acute promyelocytic leukemia (APL) are caused in part by the high expression of tissue factor (TF) on leukemic cells, which also produce TNF and IL-1β, proinflammatory cytokines known to increase TF in various cell types. Exposure of NB4 cells, an APL cell line, to all-trans retinoic acid (ATRA) or arsenic trioxide (ATO) rapidly and strongly reduced TF mRNA. Both drugs also reduced TNF mRNA, but later, and moreover increased IL-1β mRNA. The effect on procoagulant activity of cells and microparticles, as measured with calibrated automated thrombography, was delayed and only partial at 24 h...
March 25, 2017: Annals of Hematology
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