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Immune flux

Katya B Rubinow
BACKGROUND: Over the past two decades, parallel recognition has grown of the importance of both sex steroids and immune activity in metabolic regulation. More recently, these discrete areas have been integrated in studies examining the metabolic effects of sex steroid immunomodulation. Implicit in these studies has been a traditional, endocrine model of sex steroid delivery from the gonads to target cells, including immune cells. Thus, research to date has focused on the metabolic effects of sex steroid receptor signaling in immune cells...
March 8, 2018: Molecular Metabolism
Li Wang, Yang Li, Na Ning, Jin Wang, Zi Yan, Suli Zhang, Xiangying Jiao, Xiaohui Wang, Huirong Liu
It has been recognized that myocardial apoptosis is one major factor in the development of heart dysfunction and autophagy has been shown to influence the apoptosis. In previous studies, we reported that anti-β1 -adrenergic receptor autoantibodies (β1 -AABs) decreased myocardial autophagy, but the role of decreased autophagy in cardiomyocyte apoptosis remains unclear. In the present study, we used a β1 -AAB-immunized rat model to investigate the role of decreased autophagy in cardiomyocyte apoptosis. We reported that the level of autophagic flux increased early and then decreased in an actively β1 -AAB-immunized rat model...
March 14, 2018: Cell Death & Disease
Xuyao Zhang, Wei Chen, Jiajun Fan, Shaofei Wang, Zongshu Xian, Jingyun Luan, Yubin Li, Yichen Wang, Yanyang Nan, Man Luo, Song Li, Wenzhi Tian, Dianwen Ju
CD47-targeting immune checkpoint inhibitors have been investigated for immunotherapy of several cancers, glioblastoma, one of the most common tumors in brain, was still a challenge for CD47-targeting therapy. Herein, we reported novel strategies for glioblastoma therapy via blocking CD47-SIRPα by SIRPα-Fc alone or in combination with autophagy inhibition. Our results showed that SIRPα-Fc increased macrophages-triggered cytotoxicity and phagocytosis of glioblastoma cells then elicited potent anti-tumor efficacy...
March 10, 2018: Carcinogenesis
Jingjing Dai, Yong Liang, Honglin Li, Wubi Zhou, Bing Wang, Aijia Gong, Rongbo Zhang
The role of vitamin D in the regulation of lung immune defense and inflammatory response has attracted more and more attention. Vitamin D deficiency is closely related to respiratory tract infections. However, few studies have elucidated the mechanism of vitamin D deficiency on host pulmonary resistance to Aspergillus fumigatus ( A. fumigatus ). In this paper, the role of autophagy and Treg regulation in the treatment of rat models of A. fumigatus infection with vitamin D was investigated. We intratracheally injected the A...
2018: American Journal of Translational Research
Denis Martinvalet
Mitochondria and endoplasmic reticulum (ER) contact sites (MERCs) are dynamic modules enriched in subset of lipids and specialized proteins that determine their structure and functions. The MERCs regulate lipid transfer, autophagosome formation, mitochondrial fission, Ca2+ homeostasis and apoptosis. Since these functions are essential for cell biology, it is therefore not surprising that MERCs also play a critical role in organ physiology among which the immune system stands by its critical host defense function...
February 28, 2018: Cell Death & Disease
Tobias Dahm, Ortwin Adams, Sindy Boettcher, Sabine Diedrich, Vasily Morozov, Grant Hansman, Petra Fallier-Becker, Sebastian Schädler, Claus J Burkhardt, Christel Weiss, Carolin Stump-Guthier, Hiroshi Ishikawa, Horst Schroten, Christian Schwerk, Tobias Tenenbaum, Henriette Rudolph
BACKGROUND: Echovirus (E) 30 (E-30) meningitis is characterized by neuroinflammation involving immune cell pleocytosis at the protective barriers of the central nervous system (CNS). In this context, infection of the blood-cerebrospinal fluid barrier (BCSFB), which has been demonstrated to be involved in enteroviral CNS pathogenesis, may affect the tight junction (TJ) and adherens junction (AJ) function and morphology. METHODS: We used an in vitro human choroid plexus epithelial (HIBCPP) cell model to investigate the effect of three clinical outbreak strains (13-311, 13-759, and 14-397) isolated in Germany in 2013, and compared them to E-30 Bastianni...
February 20, 2018: Journal of Neuroinflammation
Marc J Tol, Martijn J C van der Lienden, Tanit L Gabriel, Jacob J Hagen, Saskia Scheij, Tineke Veenendaal, Judith Klumperman, Wilma E Donker-Koopman, Arthur J Verhoeven, Hermen Overkleeft, Johannes M Aerts, Carmen A Argmann, Marco van Eijk
In recent years, the lysosome has emerged as a highly dynamic, transcriptionally regulated organelle that is integral to nutrient-sensing and metabolic rewiring. This is coordinated by a lysosome-to-nucleus signaling nexus in which MTORC1 controls the subcellular distribution of the microphthalmia-transcription factor E (MiT/TFE) family of "master lysosomal regulators". Yet, despite the importance of the lysosome in cellular metabolism, the impact of traditional in vitro culture media on lysosomal dynamics and/or MiT/TFE localization has not been fully appreciated...
February 17, 2018: Autophagy
Changmeng Xu, Mi Wang, Zhongbao Song, Zhijian Wang, Qianyu Liu, Ping Jiang, Juan Bai, Yufeng Li, Xianwei Wang
Autophagy of cytoplasmic components plays an essential role in the pathogenic infection process. Furthermore, research suggests that autophagy is an extremely important component of the innate immune response. Our study aimed to reveal the effect of virus-induced autophagy on pseudorabies virus (PRV) replication. Our results confirmed that light chain 3 (LC3)-I was converted into LC3-II after PRV infection; this transition is considered an important indicator of autophagy. Transmission electron microscopy (TEM) revealed that PRV infection could notably increase the number of autophagosomes in mouse neuro-2a (N2a) cells...
February 13, 2018: Virus Research
Alain de Cheveigné, Dorothée Arzounian
Electroencephalography (EEG), magnetoencephalography (MEG) and related techniques are prone to glitches, slow drift, steps, etc., that contaminate the data and interfere with the analysis and interpretation. These artifacts are usually addressed in a preprocessing phase that attempts to remove them or minimize their impact. This paper offers a set of useful techniques for this purpose: robust detrending, robust rereferencing, outlier detection, data interpolation (inpainting), step removal, and filter ringing artifact removal...
February 12, 2018: NeuroImage
Pallavi Varshney, Neeru Saini
Psoriasis is an immune-mediated inflammatory disease of the skin. Previous studies including ours have shown that IL-17A plays a major role in its pathogenesis; however, its precise molecular mechanism of action is not well understood. Cytokines like TNF α and IL-23 are also important in mediating the disease and some studies have also reported autophagy as a novel mechanism by which cytokines controls the immune response. Herein, we investigated the effect of IL-17A on autophagy and reveal crosstalk between autophagy and cholesterol signaling in keratinocytes...
February 9, 2018: Biochimica et Biophysica Acta
W J M Janssen, V Grobarova, J Leleux, C H Jongeneel, M van Gijn, J M van Montfrans, M Boes
BACKGROUND: PSTPIP1 is a cytosolic adaptor protein involved with T-cell activation, differentiation, and migration. Upon cognate T-cell contact, PSTPIP1 is recruited to surface-expressed CD2, where it regulates f-actin remodeling. An immune synapse (IS) is thereby rapidly formed, consisting of TCR clusters surrounded by a ring of adhesion molecules including CD2. OBJECTIVE: From genetic screening of primary immunodeficiency patients, we identified two mutations in PSTPIP1, R228C and T274M which we further characterized in primary patient T-cells...
February 9, 2018: Journal of Allergy and Clinical Immunology
Jennifer L J Heaney, Sophie C Killer, Ida S Svendsen, Michael Gleeson, John P Campbell
Periods of short-term intensified training (IT) are often used by athletes during training cycles over the season and undergoing phases of increased physical stress may impact upon the immune system. This study investigated the effects of a period of IT on free light chains (FLCs) in saliva - an emerging immune biomarker of oral inflammation - and matched serum samples in well-trained athletes. It also examined if IT influences basal FLC levels and FLC flux during acute exercise. Highly trained male cyclists (n = 10) underwent a 9-day period of IT; before and after IT participants performed a 1 h time trial (TT) on a cycle ergometer, with blood and saliva samples collected pre- and post-exercise...
February 7, 2018: Physiology & Behavior
Chia-Wei Hsieh, Chun-Yu Chang, Yi-Ming Chen, Hsin-Hua Chen, Wei-Ting Hung, Ning-Rong Gung, Shiow-Jiuan Wey, Der-Yuan Chen
The pathogenic role of autophagic immune regulation in adult-onset Still's disease (AOSD) is unclear. We investigated the relative levels of autophagy in AOSD patients and healthy controls, its association with disease activity or course, and the change in autophagy after 6 months of therapy. Autophagosome levels were determined from the mean fluorescence intensity of autophagosomotropic dye incorporated into circulating immune cells. The fluorescent signal from lymphocytes, monocytes, and granulocytes from AOSD patients was greater than from controls...
January 2, 2018: Oncotarget
Pedro Bullón, Beatriz Castejón-Vega, Lourdes Román-Malo, María Paz Jimenez-Guerrero, David Cotán, Tamara Y Forbes-Hernandez, Alfonso Varela-López, Antonio Pérez-Pulido, Francesca Giampieri, José L Quiles, Maurizio Battino, José A Sánchez-Alcázar, Mario D Cordero
BACKGROUND: Cathepsin C (CatC) is a lysosomal enzyme involved in the activation of serine proteases from immune and inflammatory cells. Several mutations with loss of function in the Cathepsin C (CatC) gene have been shown to be the genetic mark of Papillon-Lefèvre syndrome (PLS), a rare autosomal recessive disease characterized by severe early-onset periodontitis, palmoplantar hyperkeratosis and increased susceptibility to infections. Deficiencies or dysfunction in other cathepsin family proteins such as B or D have been associated with autophagic and lysosomal disorders...
February 1, 2018: Journal of Allergy and Clinical Immunology
Ayano Kabashima, Petra Hirsova, Steven F Bronk, Matthew C Hernandez, Mark J Truty, Sumera Rizvi, Scott H Kaufmann, Gregory J Gores
BACKGROUND & AIMS: Myeloid cell leukemia1 (MCL1), a prosurvival member of the BCL2 protein family, plays a pivotal role in human cholangiocarcinoma (CCA) cell survival. We have previously reported that fibroblast growth factor receptor (FGFR) signaling mediates MCL1-dependent survival of CCA cells in vitro and in vivo. However, the mode and mechanisms of cell death in this model were not delineated. METHODS: Human CCA cell lines were treated with the pan-FGFR inhibitor LY2874455 and the mode of cell death examined by several complementary assays...
February 2, 2018: Journal of Hepatology
Kimberly J Reidy, Rebecca Hjorten, Rulan S Parekh
PURPOSE OF REVIEW: Understanding the genetic risk of APOL1 in children and young adults is important given the lifetime risk of hypertension and kidney disease among children of African descent. We review recent epidemiologic and biologic findings on the effects of APOL1 and kidney disease. RECENT FINDINGS: APOL1 in children and young adults is associated with hypertension, albuminuria and more rapid decline in kidney function and progression to end-stage kidney disease, especially among those with glomerular causes of kidney disease, and those affected by sickle cell disease or HIV...
February 5, 2018: Current Opinion in Pediatrics
Miranda Machacek, Chad Slawson, Patrick E Fields
The rapidly expanding field of immunometabolism focuses on how metabolism controls the function of immune cells. CD4+ T cells are essential for the adaptive immune response leading to the eradication of specific pathogens. However, when T cells are inappropriately over-active, they can drive autoimmunity, allergic disease, and chronic inflammation. The mechanisms by which metabolic changes influence function in CD4+ T cells are not fully understood. The post-translational protein modification, O-GlcNAc (O-linked β-N-acetylglucosamine), dynamically cycles on and off of intracellular proteins as cells respond to their environment and flux through metabolic pathways changes...
February 6, 2018: Journal of Bioenergetics and Biomembranes
R A Pederzolli, A G Van Kessel, J Campbell, S Hendrick, K M Wood, G B Penner
The objective of this study was to determine effect of ruminal acidosis and low feed intake on the regional barrier function of the gastrointestinal tract. Twenty-one Holstein steers were fed for ad libitum intake for 5 d (CON), fed at 25% of ad libitum intake for 5 d (LFI), or provided 2 d of ad libitum intake follows by 1-d of feed restriction (25% of ad libitum intake), 1 day where 30% of ad libitum DMI was provided as pelleted barley followed by the full allocation (RA) and fed for ad libitum intake the following day...
January 29, 2018: Journal of Animal Science
Martine Lambelet, Leticia F Terra, Makiko Fukaya, Kira Meyerovich, Leticia Labriola, Alessandra K Cardozo, Florent Allagnat
Type 1 diabetes (T1D) results from β-cell destruction due to concerted action of both innate and adaptive immune responses. Pro-inflammatory cytokines, such as interleukin-1β and interferon-γ, secreted by the immune cells invading islets of Langerhans, contribute to pancreatic β-cell death in T1D. Cytokine-induced endoplasmic reticulum (ER) stress plays a central role in β-cell demise. ER stress can modulate autophagic response; however, no study addressed the regulation of autophagy during the pathophysiology of T1D...
January 24, 2018: Cell Death & Disease
Lamia Harper, Divya Balasubramanian, Elizabeth A Ohneck, William E Sause, Jessica Chapman, Bryan Mejia-Sosa, Tenzin Lhakhang, Adriana Heguy, Aristotelis Tsirigos, Beatrix Ueberheide, Jeffrey M Boyd, Desmond S Lun, Victor J Torres
Staphylococcus aureus is a versatile bacterial pathogen that can cause significant disease burden and mortality. Like other pathogens, S. aureus must adapt to its environment to produce virulence factors to survive the immune responses evoked by infection. Despite the importance of environmental signals for S. aureus pathogenicity, only a limited number of these signals have been investigated in detail for their ability to modulate virulence. Here we show that pyruvate, a central metabolite, causes alterations in the overall metabolic flux of S...
January 23, 2018: MBio
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