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https://www.readbyqxmd.com/read/28732079/lmp1-mediated-glycolysis-induces-myeloid-derived-suppressor-cell-expansion-in-nasopharyngeal-carcinoma
#1
Ting-Ting Cai, Shu-Biao Ye, Yi-Na Liu, Jia He, Qiu-Yan Chen, Hai-Qiang Mai, Chuan-Xia Zhang, Jun Cui, Xiao-Shi Zhang, Pierre Busson, Yi-Xin Zeng, Jiang Li
Myeloid-derived suppressor cells (MDSCs) are expanded in tumor microenvironments, including that of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). The link between MDSC expansion and EBV infection in NPC is unclear. Here, we show that EBV latent membrane protein 1 (LMP1) promotes MDSC expansion in the tumor microenvironment by promoting extra-mitochondrial glycolysis in malignant cells, which is a scenario for immune escape initially suggested by the frequent, concomitant detection of abundant LMP1, glucose transporter 1 (GLUT1) and CD33+ MDSCs in tumor sections...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28730954/evaluation-of-in-vitro-anti-psoriatic-activity-of-a-novel-polyherbal-formulation-by-multiparametric-analysis
#2
Nadav Shraibom, Alka Madaan, Vidushi Joshi, Ritu Verma, Anika Chaudhary, Gautam Mishra, Anshumali Awasthi, Anu Taneja Singh, Manu Jaggi
The beneficial role of traditional herbal medicines in the treatment of inflammatory skin disorders has been widely reported. Psoriasis is characterized by uncontrolled hyper-proliferation of keratinocytes, disturbed apoptosis, over-secretion of inflammatory cytokines and angiogenic factors. We have developed a novel aqueous polyherbal formulation (SIRB-001) consisting of 3 herbs; Rheum palmatum L., Rehmannia glutinosa Libosch and Lonicera Japonica in the ratio 1:1:3. SIRB-001 has demonstrated efficacious effects in psoriasis patients...
July 20, 2017: Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28729539/comparative-proteomic-analysis-of-human-embryonic-stem-cell-derived-and-primary-human-retinal-pigment-epithelium
#3
Heidi Hongisto, Antti Jylhä, Janika Nättinen, Jochen Rieck, Tanja Ilmarinen, Zoltán Veréb, Ulla Aapola, Roger Beuerman, Goran Petrovski, Hannu Uusitalo, Heli Skottman
Human embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE) provide an unlimited cell source for retinal cell replacement therapies. Clinical trials using hESC-RPE to treat diseases such as age-related macular degeneration (AMD) are currently underway. Human ESC-RPE cells have been thoroughly characterized at the gene level but their protein expression profile has not been studied at larger scale. In this study, proteomic analysis was used to compare hESC-RPE cells differentiated from two independent hESC lines, to primary human RPE (hRPE) using Isobaric tags for relative quantitation (iTRAQ)...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729291/stimulator-of-ifn-genes-mediated-dna-sensing-pathway-is-suppressed-by-nlrp3-agonists-and-regulated-by-mitofusin-1-and-tbc1d15-mitochondria-dynamics-mediators
#4
Dohyeong Kwon, Eunbyeol Park, Suk-Jo Kang
The stimulator of IFN genes (STING)-mediated DNA-sensing pathway plays an important role in the innate immune response to pathogen infection, autoimmunity, and cancer; however, its regulatory mechanism has not been fully elucidated, and we do not yet know whether the STING pathway is counter-regulated by other innate immune pathways. Here, we show that the NLRP3-activating agonists, ATP and nigericin, prevent STING pathway activation in association with mitochondrial fragmentation; however, the suppression of the STING pathway and mitochondria fission were not dependent on NLRP3 or potassium efflux...
July 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28723682/release-of-danger-associated-molecular-patterns-following-chemotherapy-does-not-induce-immunoparalysis-in-leukemia-patients
#5
Kim Timmermans, Guus P Leijte, Matthijs Kox, Gert Jan Scheffer, Nicole M A Blijlevens, Peter P Pickkers
Chemotherapy may result in the release of danger-associated molecular patterns (DAMPs), which can cause immunoparalysis (deactivation of the immune system). We investigated DAMPs following chemotherapy and their relationship with markers of immunoparalysis in leukemia patients. In 6 patients with acute myeloid leukemia or myelodysplastic syndrome and 12 healthy subjects, DAMPs, cytokines, and markers of immunoparalysis were determined before and during the first week after chemotherapy initiation. In the patients, plasma levels of nuclear DNA (a marker of general DAMP release) were profoundly increased before chemotherapy and further increased 4-6 h afterwards, while the specific DAMP mitochondrial DNA showed only a trend towards increase...
July 20, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/28717359/the-c-terminal-effector-domain-of-non-structural-protein-1-of-influenza-a-virus-blocks-ifn-%C3%AE-production-by-targeting-tnf-receptor-associated-factor-3
#6
Wei Qian, Xiaoqin Wei, Kelei Guo, Yongtao Li, Xian Lin, Zhong Zou, Hongbo Zhou, Meilin Jin
Influenza A virus non-structural protein 1 (NS1) antagonizes interferon response through diverse strategies, particularly by inhibiting the activation of interferon regulatory factor 3 (IRF3) and IFN-β transcription. However, the underlying mechanisms used by the NS1 C-terminal effector domain (ED) to inhibit the activation of IFN-β pathway are not well understood. In this study, we used influenza virus subtype of H5N1 to demonstrate that the NS1 C-terminal ED but not the N-terminal RNA-binding domain, binds TNF receptor-associated factor 3 (TRAF3)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28715601/methamphetamine-increases-prion-protein-and-induces-dopamine-dependent-expression-of-protease-resistant-prpsc
#7
M Ferrucci, L Ryskalin, F Biagioni, S Gambardella, C L Busceti, A Falleni, G Lazzeri, F Fornai
The cellular prion protein (PrPc) is physiologically expressed within selective brain areas of mammals. Alterations in the secondary structure of this protein lead to scrapie-like prion protein (PrPsc), which precipitates in the cell. PrPsc has been detected in infectious, inherited or sporadic neurodegenerative disorders. Prion protein metabolism is dependent on autophagy and ubiquitin proteasome. Despite not being fully elucidated, the physiological role of prion protein relates to chaperones which rescue cells under stressful conditions...
July 1, 2017: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/28713392/il-15-harnesses-pro-inflammatory-function-of-temra-cd8-in-kidney-transplant-recipients
#8
Gaëlle Tilly, Tra-My Doan-Ngoc, Michelle Yap, Aurélie Caristan, Lola Jacquemont, Richard Danger, Marion Cadoux, Sarah Bruneau, Magali Giral, Pierrick Guerif, Bryan Nicol, Alexandra Garcia, David-Axel Laplaud, Sophie Brouard, Claire Pecqueur Hellman, Nicolas Degauque
The involvement of TEMRA CD8 is evident in a large array of immunological conditions ranging from auto- to allo-immunity. Nevertheless, the factors leading to their accumulation and activation remain ill-defined and, efficient therapeutics to control their inflammatory response is lacking. Here, we show that IL-15-stimulated TEMRA from kidney-transplant (KT) recipients promote inflammation by inducing the expression of CX3CL1 by endothelial cells in an IFN-γ- and TNF-α-dependent manner. The responsiveness of TEMRA to IL-15 is not restricted to chronic stimulation, as TEMRA from healthy volunteers respond earlier and faster when compared to effector memory (EM)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28710430/rlr-mediated-antiviral-innate-immunity-requires-oxidative-phosphorylation-activity
#9
Takuma Yoshizumi, Hiromi Imamura, Tomohiro Taku, Takahiro Kuroki, Atsushi Kawaguchi, Kaori Ishikawa, Kazuto Nakada, Takumi Koshiba
Mitochondria act as a platform for antiviral innate immunity, and the immune system depends on activation of the retinoic acid-inducible gene I (RIG-I)-like receptors (RLR) signaling pathway via an adaptor molecule, mitochondrial antiviral signaling. We report that RLR-mediated antiviral innate immunity requires oxidative phosphorylation (OXPHOS) activity, a prominent physiologic function of mitochondria. Cells lacking mitochondrial DNA or mutant cells with respiratory defects exhibited severely impaired virus-induced induction of interferons and proinflammatory cytokines...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28703078/chrysophanol-suppresses-pro-inflammatory-response-in-microglia-via-regulation-of-drp1-dependent-mitochondrial-fission
#10
Unbin Chae, Ju-Sik Min, Hanna Lee, Kyung-Sik Song, Hyun-Shik Lee, Hong Jun Lee, Sang-Rae Lee, Dong-Seok Lee
OBJECTIVES: Chrysophanol, also called chrysophanic acid, is a natural anthraquinone compound found in Rheum palmatum. R. palmatum has been used in oriental medicine in ancient East Asia. Microglial cells represent not only the forefront immune defense in the central nervous system but also the most reactive sensors to various threats. However, activated microglia can exert neurotoxic effects via excessive production of cytotoxic molecules and proinflammatory cytokines. Therefore, modulation of microglial cell activation is important for maintaining neuronal function...
July 13, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28692767/reactive-oxygen-species-regulating-polymersome-as-an-antiviral-agent-against-influenza-virus
#11
Hyun-Ouk Kim, Minjoo Yeom, Jihye Kim, Aastha Kukreja, Woonsung Na, Jihye Choi, Aram Kang, Dayeon Yun, Jong-Woo Lim, Daesub Song, Seungjoo Haam
Reactive oxygen species (ROS) produced during mitochondrial oxidative phosphorylation play an important role as signal messengers in the immune system and also regulate signal transduction. ROS production, initiated as a consequence of microbial invasion, if generated at high levels, induces activation of the MEK (mitogen-activated protein kinase kinase)/ERK (extracellular signal-regulated kinase) pathway to promote cell survival and proliferation. However, viruses hijack the host cells' pathways, causing biphasic activation of the MEK/ERK cascade...
July 10, 2017: Small
https://www.readbyqxmd.com/read/28690610/toll-like-receptor-4-inhibition-improves-oxidative-stress-and-mitochondrial-health-in-isoproterenol-induced-cardiac-hypertrophy-in-rats
#12
Parmeshwar B Katare, Pankaj K Bagul, Amit K Dinda, Sanjay K Banerjee
BACKGROUND: Inflammation remains a crucial factor for progression of cardiac diseases and cardiac hypertrophy remains an important cause of cardiac failure over all age groups. As a key regulator of inflammation, toll-like receptor 4 (TLR4) plays an important role in pathogenesis of cardiac diseases. Being an important regulator of innate immunity, the precise pathway of TLR4-mediated cardiac complications is yet to be established. Therefore, the primary objective of the present study was to find the role of TLR4 in cardiac hypertrophy and the molecular mechanism thereof...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28685960/platelet-derived-mitochondria-display-embryonic-stem-cell-markers-and-improve-pancreatic-islet-%C3%AE-cell-function-in-humans
#13
Yong Zhao, Zhaoshun Jiang, Elias Delgado, Heng Li, Huimin Zhou, Wei Hu, Marcos Perez-Basterrechea, Anna Janostakova, Qidong Tan, Jing Wang, Mao Mao, Zhaohui Yin, Ye Zhang, Ying Li, Quanhai Li, Jing Zhou, Yunxiang Li, Eva Martinez Revuelta, Jose Maria García-Gala, Honglan Wang, Silvia Perez-Lopez, Maria Alvarez-Viejo, Edelmiro Menendez, Thomas Moss, Edward Guindi, Jesus Otero
Diabetes is a major global health issue and the number of individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) increases annually across multiple populations. Research to develop a cure must overcome multiple immune dysfunctions and the shortage of pancreatic islet β cells, but these challenges have proven intractable despite intensive research effort more than the past decades. Stem Cell Educator (SCE) therapy-which uses only autologous blood immune cells that are externally exposed to cord blood stem cells adhering to the SCE device, has previously been proven safe and effective in Chinese and Spanish subjects for the improvement of T1D, T2D, and other autoimmune diseases...
July 7, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28685841/krebs-cycle-rewired-for-macrophage-and-dendritic-cell-effector-functions
#14
REVIEW
D G Ryan, L A O'Neill
The Krebs cycle is an amphibolic pathway operating in the mitochondrial matrix of all eukaryotic organisms. In response to pro-inflammatory stimuli, macrophages and dendritic cells undergo profound metabolic remodelling to support the biosynthetic and bioenergetic requirements of the cell. Recently it has been discovered that this metabolic shift also involves the rewiring of the Krebs cycle to regulate cellular metabolic flux and the accumulation of Krebs cycle intermediates, notably, citrate, succinate and fumarate...
July 7, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28683296/inflammasomes-on-the-crossroads-of-innate-immune-recognition-and-metabolic-control
#15
REVIEW
Tomasz Próchnicki, Eicke Latz
Inflammasomes are protein complexes formed upon encounter of microbial or damage-associated stimuli. The main output of inflammasome assembly is activation of caspase-1, a protease involved in both pro-inflammatory and host-protective responses. Defined bacterial or viral ligands have been identified for the inflammasome-forming receptors AIM2, NLRP1, and NLRC4. The signals activating other inflammasomes, NLRP3, NLRP6, and pyrin, are less well understood. Recent studies implicated several low-molecular-weight compounds traditionally linked to metabolism, not immunity, in modulation of inflammasome signaling...
July 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28682614/total-synthesis-of-cardiolipins-containing-chiral-cyclopropane-fatty-acids
#16
Shinsuke Inuki, Ippei Ohta, Shunichi Ishibashi, Masayuki Takamatsu, Koichi Fukase, Yukari Fujimoto
Cardiolipin (CL) is a phospholipid located in both the eukaryotic mitochondrial inner membrane and the bacterial cell membrane. Some bacterial CLs are known to contain cyclopropane moieties in their acyl chains. Although the CLs are thought to be involved in the innate immune response, there have been few attempts at chemical synthesis of the CLs, and detailed studies of their biological activities. Thus, we have developed a synthetic route to CLs containing chiral cyclopropane moieties.
July 6, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28680969/differential-antagonism-of-human-innate-immune-responses-by-tick-borne-phlebovirus-nonstructural-proteins
#17
Veronica V Rezelj, Ping Li, Vidyanath Chaudhary, Richard M Elliott, Dong-Yan Jin, Benjamin Brennan
In recent years, several newly discovered tick-borne viruses causing a wide spectrum of diseases in humans have been ascribed to the Phlebovirus genus of the Bunyaviridae family. The nonstructural protein (NSs) of bunyaviruses is the main virulence factor and interferon (IFN) antagonist. We studied the molecular mechanisms of IFN antagonism employed by the NSs proteins of human apathogenic Uukuniemi virus (UUKV) and those of Heartland virus (HRTV) and severe fever with thrombocytopenia syndrome virus (SFTSV), both of which cause severe disease...
May 2017: MSphere
https://www.readbyqxmd.com/read/28669986/mitochondrial-control-of-immunity-beyond-atp
#18
REVIEW
Manan M Mehta, Samuel E Weinberg, Navdeep S Chandel
Mitochondria are important signalling organelles, and they dictate immunological fate. From T cells to macrophages, mitochondria form the nexus of the various metabolic pathways that define each immune cell subset. In this central position, mitochondria help to control the various metabolic decision points that determine immune cell function. In this Review, we discuss how mitochondrial metabolism varies across different immune cell subsets, how metabolic signalling dictates cell fate and how this signalling could potentially be targeted therapeutically...
July 3, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28668382/inflammation-and-mitochondrial-dysfunction-a-vicious-circle-in-neurodegenerative-disorders
#19
REVIEW
Jack van Horssen, Pauline van Schaik, Maarten Witte
Experimental evidence supports an intricate association between inflammation and mitochondrial dysfunction as main contributors of neurological diseases. Inflammatory mediators produced by activated microglia and infiltrated immune cells trigger intracellular signaling cascades that can alter cellular mitochondrial metabolism. Cytokines, particularly tumor necrosis factor-alpha, impede mitochondrial oxidative phosphorylation and associated ATP production and instigate mitochondrial reactive oxygen species production...
June 28, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28667492/inflammation-cause-or-consequence-of-heart-failure-or-both
#20
REVIEW
Sophie Van Linthout, Carsten Tschöpe
PURPOSE OF REVIEW: With the intention to summarize the currently available evidence on the pathophysiological relevance of inflammation in heart failure, this review addresses the question whether inflammation is a cause or consequence of heart failure, or both. RECENT FINDINGS: This review discusses the diversity (sterile, para-inflammation, chronic inflammation) and sources of inflammation and gives an overview of how inflammation (local versus systemic) can trigger heart failure...
June 30, 2017: Current Heart Failure Reports
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