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mitochondrial immunity

Qin Jiang, Xiyue Li, Shanshan Cheng, Yuxiu Gu, Gui Chen, Yuexin Shen, Yixi Xie, Yi Cao
We have recently proposed that the interaction between food components and nanoparticles (NPs) should be considered when evaluating the toxicity of NPs. In the present study, we used THP-1 differentiated macrophages as a model for immune cells and investigated the combined toxicity of low levels of palmitate (PA; 10 or 50μM) and ZnO NPs. The results showed that PA especially at 50μM changed the size, Zeta potential and UV-vis spectra of ZnO NPs, indicating a possible coating effect. Up to 32μg/mL ZnO NPs did not significantly affect mitochondrial activity, intracellular reactive oxygen species (ROS) or release of interleukin 6 (IL-6), but significantly impaired lysosomal function as assessed by neutral red uptake assay and acridine orange staining...
October 18, 2016: Environmental Toxicology and Pharmacology
Olena Odnokoz, Kyle Nakatsuka, Vladimir I Klichko, Jacqueline Nguyen, Liz Calderon Solis, Kaitlin Ostling, Marziyeh Badinloo, William C Orr, Svetlana N Radyuk
Previously, we have shown that flies under-expressing the two mitochondrial peroxiredoxins (Prxs), dPrx3 and dPrx5, display increases in tissue-specific apoptosis and dramatically shortened life span, associated with a redox crisis, manifested as changes in GSH:GSSG and accumulation of protein mixed disulfides. To identify specific pathways responsible for the observed biological effects, we performed a transcriptome analysis. Functional clustering revealed a prominent group enriched for immunity-related genes, including a considerable number of NF-kB-dependent antimicrobial peptides (AMP) that are up-regulated in the Prx double mutant...
October 19, 2016: Biochimica et Biophysica Acta
Javier Ochoa-Repáraz, Sara L Colpitts, Christopher Kircher, Eli J Kasper, Kiel M Telesford, Sakhina Begum-Haque, Anudeep Pant, Lloyd H Kasper
OBJECTIVE: To determine whether as an orally delivered treatment, teriflunomide, an inhibitor of the mitochondrial enzyme dihydroorotate dehydrogenase approved to treat relapsing forms of multiple sclerosis, could affect gut-associated lymphoid tissue (GALT) immune responses functionally. METHODS: C57BL/6 mice were treated orally with teriflunomide and flow cytometric analysis of immune GALT cells performed ex vivo, and adoptive transfer experiments were used to test the protective effects of GALT regulatory T (Treg) cells...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
Mohammad Iqbal Lone, Arisa Nabi, Nawab John Dar, Aashiq Hussain, Nazia Nazam, Abid Hamid, Waseem Ahmad
Dichlorophene; a halogenated phenolic compound with wide applications as a fungicide, bactericide and antiprotozoan. Dichlorophene spray also has therapeutic use in the disease digital dermatitis. In guinea pigs, a few studies obtained mixed results in dicholorophene sensitization tests. In consideration of the fact, that the mechanism of its genotoxicity has not been adequately elucidated lead to present study assessing the acute in vivo toxicological impact in Rattus norvegicus. A systematic research has been made encompassing the use of molecular and flow cytometric approaches...
October 17, 2016: Chemosphere
Alan Pestronk, Richard Keeling, Rati Choksi
OBJECTIVE: We studied mitochondrial impairment as a factor in the pathologic equivalent of sarcopenia, muscle fiber atrophy associated with increased age. METHODS: Mitochondrial oxidative enzyme activities and coenzyme Q10 levels were measured in frozen human proximal limb muscles with combined age and atrophy, age alone, atrophy alone, denervation, immune myopathies, and mitochondrial disorders with ophthalmoplegia. RESULTS: Sarcopenia (age and atrophy) had reduced mean activities of mitochondrial Complexes I, II, and II+III, with severe reduction of Complex I activity in 54% of patients...
October 19, 2016: Muscle & Nerve
Mei-Mei Gu, Jing-Rong Kong, Di-Huang, Ting Peng, Chen-Ying Xie, Kai-Yuan Yang, Yuan Liu, Wei-Na Wang
Prohibitin2 (PHB2), a potential tumor suppressor protein, plays important roles in inhibition of cell cycle progression, transcriptional regulation, apoptosis and the mitochondrial respiratory chain. To explore its potential roles in crustaceans' immune responses we have identified and characterized LvPHB2, a 891 bp gene encoding a 297 amino acids protein in the shrimp Litopenaeus vannamei. Expression analyses showed that LvPHB2 is expressed in all examined tissues, and largely present in cytoplasm, correlating with its known anti-oxidation function in mitochondria...
October 15, 2016: Developmental and Comparative Immunology
Christian Adam, Jonas Wohlfarth, Maike Haußmann, Helga Sennefelder, Annette Rodin, Mareike Maler, Stefan F Martin, Matthias Goebeler, Marc Schmidt
Chromium allergy is a common occupational skin disease mediated by chromium (VI)-specific T cells that induce delayed-type hypersensitivity in sensitized individuals. Additionally, chromium (VI) can act as irritant. Both responses critically require innate immune activation, but if and how chromium (VI) elicits this signal is currently unclear.Using human monocytes, primary human keratinocytes and murine dendritic cells we show that chromium (VI) compounds fail to trigger direct proinflammatory activation but potently induce processing and secretion of IL-1β...
October 14, 2016: Journal of Investigative Dermatology
Kuo Du, Anup Ramachandran, Hartmut Jaeschke
Acetaminophen (APAP) hepatotoxicity is characterized by an extensive oxidative stress. However, its source, pathophysiological role and possible therapeutic potential if targeted, have been controversially described. Earlier studies argued for cytochrome P450-generated reactive oxygen species (ROS) during APAP metabolism, which resulted in massive lipid peroxidation and subsequent liver injury. However, subsequent studies convincingly challenged this assumption and the current paradigm suggests that mitochondria are the main source of ROS, which impair mitochondrial function and are responsible for cell signaling resulting in cell death...
October 4, 2016: Redox Biology
Yu Chen, Xiaoling Deng, Junfang Deng, Jiehua Zhou, Yuping Ren, Shengxuan Liu, Deborah J Prusak, Thomas G Wood, Xiaoyong Bao
Human metapneumovirus (hMPV) is a major cause of lower respiratory infection in young children. Repeated infections occur throughout life, but its immune evasion mechanisms are largely unknown. We recently found that hMPV M2-2 protein elicits immune evasion by targeting mitochondrial antiviral-signaling protein (MAVS), an antiviral signaling molecule. However, the molecular mechanisms underlying such inhibition are not known. Our mutagenesis studies revealed that PDZ-binding motifs, 29-DEMI-32 and 39-KEALSDGI-46, located in an immune inhibitory region of M2-2, are responsible for M2-2-mediated immune evasion...
October 13, 2016: Virology
Hector A Cabrera-Fuentes, Julian Aragones, Jürgen Bernhagen, Andreas Boening, William A Boisvert, Hans E Bøtker, Heerajnarain Bulluck, Stuart Cook, Fabio Di Lisa, Felix B Engel, Bernd Engelmann, Fulvia Ferrazzi, Péter Ferdinandy, Alan Fong, Ingrid Fleming, Erich Gnaiger, Sauri Hernández-Reséndiz, Siavash Beikoghli Kalkhoran, Moo Hyun Kim, Sandrine Lecour, Elisa A Liehn, Michael S Marber, Manuel Mayr, Tetsuji Miura, Sang-Bing Ong, Karlheinz Peter, Daniel Sedding, Manvendra K Singh, M Saadeh Suleiman, Hans J Schnittler, Rainer Schulz, Winston Shim, Daniel Tello, Carl-Wilhelm Vogel, Malcolm Walker, Qilong Oscar Yang Li, Derek M Yellon, Derek J Hausenloy, Klaus T Preissner
In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients' cohorts, the influence of co-morbidities and medications, as well as the contribution of innate immune reactions in cardioprotection. Moreover, developmental or systems biology approaches bear great potential in systematically uncovering unexpected components involved in ischemia-reperfusion injury or heart regeneration...
November 2016: Basic Research in Cardiology
Young Bong Choi, Noula Shembade, Kislay Parvatiyar, Siddharth Balachandran, Edward William Harhaj
The host response to RNA virus infection consists of an intrinsic innate immune response and the induction of apoptosis as mechanisms to restrict viral replication. The mitochondrial adaptor molecule MAVS plays critical roles in coordinating both virus-induced type I interferon production and apoptosis; however, the regulation of MAVS-mediated apoptosis is poorly understood. Here, we show that the adaptor protein TAX1BP1 functions as a negative regulator of virus-induced apoptosis. TAX1BP1-deficient cells are highly sensitive to apoptosis in response to infection with the RNA viruses vesicular stomatitis virus and Sendai virus and transfection with poly(I:C)...
October 10, 2016: Molecular and Cellular Biology
Gang Deng, Shifang Yu, Qiming Li, Yunlei He, Wei Liang, Lu Yu, Deyi Xu, Tao Sun, Ri Zhang, Qiang Li
OBJECTIVES: Immune thrombocytopenia (ITP) is an acquired and heterogeneous autoimmune-mediated hematological disease typically characterized by a low platelet count. Emerging evidence over the past several years suggests that platelet biogenesis and ageing are regulated, at least in part, by apoptotic mechanisms. However, the association between decreased platelets and apoptosis in ITP patients is poorly understood. To better understand the role of platelet apoptosis in ITP pathophysiology, we investigated apoptotic markers in platelets acquired from 40 chronic ITP patients...
October 13, 2016: Hematology (Amsterdam, Netherlands)
Julien Moretti, J Magarian Blander
The innate immune response of phagocytes to microbes has long been known to depend on the core signaling cascades downstream of pattern recognition receptors (PRRs), which lead to expression and production of inflammatory cytokines that counteract infection and induce adaptive immunity. Cell-autonomous responses have recently emerged as important mechanisms of innate immunity. Either IFN-inducible or constitutive, these processes aim to guarantee cell homeostasis but have also been shown to modulate innate immune response to microbes and production of inflammatory cytokines...
October 12, 2016: Journal of Leukocyte Biology
Nathaniel B Bone, Zhongyu Liu, Jean-Francois Pittet, Jaroslaw W Zmijewski
Catecholamines, including β-adrenergic and dopaminergic neurotransmitters, have an essential role in regulating the "fight or flight" reflex and also affects immune cell proinflammatory action. However, little is known about whether catecholamines prevent dysfunction of metabolic pathways associated with inflammatory organ injury, including development of acute lung injury (ALI). We hypothesize that selected catecholamines may reduce metabolic alterations in LPS-stimulated macrophages and in the lungs of mice subjected to endotoxin-induced ALI, a situation characterized by diminished activity of AMP-activated protein kinase (AMPK)...
October 12, 2016: Journal of Leukocyte Biology
Jan Van den Bossche, Jeroen Baardman, Natasja A Otto, Saskia van der Velden, Annette E Neele, Susan M van den Berg, Rosario Luque-Martin, Hung-Jen Chen, Marieke C S Boshuizen, Mohamed Ahmed, Marten A Hoeksema, Alex F de Vos, Menno P J de Winther
Macrophages are innate immune cells that adopt diverse activation states in response to their microenvironment. Editing macrophage activation to dampen inflammatory diseases by promoting the repolarization of inflammatory (M1) macrophages to anti-inflammatory (M2) macrophages is of high interest. Here, we find that mouse and human M1 macrophages fail to convert into M2 cells upon IL-4 exposure in vitro and in vivo. In sharp contrast, M2 macrophages are more plastic and readily repolarized into an inflammatory M1 state...
October 11, 2016: Cell Reports
Herbert Tilg, Alexander R Moschen, Michael Roden
The liver constitutes a key organ in systemic metabolism, contributing substantially to the development of insulin resistance and type 2 diabetes mellitus (T2DM). The mechanisms underlying these processes are not entirely understood, but involve hepatic fat accumulation, alterations of energy metabolism and inflammatory signals derived from various cell types including immune cells. Lipotoxins, mitochondrial function, cytokines and adipocytokines have been proposed to play a major part in both NAFLD and T2DM...
October 12, 2016: Nature Reviews. Gastroenterology & Hepatology
Sarah Fogleman, Casey Santana, Casey Bishop, Alyssa Miller, David G Capco
Thousands of mothers are at risk of transmitting mitochondrial diseases to their offspring each year, with the most severe form of these diseases being fatal [1]. With no cure, transmission prevention is the only current hope for decreasing the disease incidence. Current methods of prevention rely on low mutant maternal mitochondrial DNA levels, while those with levels close to or above threshold (>60%) are still at a very high risk of transmission [2]. Two novel approaches may offer hope for preventing and treating mitochondrial disease: mitochondrial replacement therapy, and CRISPR/Cas9...
2016: American Journal of Stem Cells
Sebastian Schnitzler, Jürgen Kopitz, Konstanze Plaschke
OBJECTIVE: The role of inflammation in cognitive alterations in a post-operative setting is still not fully understood. Surgical interventions can cause systemic inflammations which eventually can induce neuroinflammation. However, the main causes of functional changes after surgery are still elusive. In this study, we investigated the role of CD38, a TNFα-inducible NADH(+) cyclase and hydrolase. We assume that CD38 overexpression impairs mitochondrial ATP synthesis. Within the hippocampus, the resulting cellular death could lead to cognitive impairment...
October 11, 2016: Neurological Research
Dariusz Andrzejczak, Agata Woldan-Tambor, Katarzyna Bednarska, Jolanta B Zawilska
A growing body of evidence suggests that inflammatory processes and activation of glial cells could contribute to seizures and epileptogenesis. In various animal studies on epilepsy, proinflammatory cytokines have been demonstrated to exert a proconvulsive activity. On the other hand, it is suggested that antiepileptic drugs could modulate immune system activity. The aim of the present study was to investigate whether topiramate, a new generation antiepileptic drug with a complex mechanism of action, could affect the lipopolysaccharide (LPS)-induced release of TNF-α, IL-1β and IL-6 from primary rat microglial cell cultures...
September 28, 2016: Epilepsy Research
Ning Li, Tianqi Hong, Rong Li, Yao Wang, Mengjiao Guo, Zongxi Cao, Yumei Cai, Sidang Liu, Tongjie Chai, Liangmeng Wei
Mitochondrial antiviral-signaling protein (MAVS), an adaptor protein of retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs)-mediated signal pathway, is involved in innate immunity. In this study, Cherry Valley duck MAVS (duMAVS) was cloned from the spleen and analyzed. duMAVS was determined to have a caspase activation and recruitment domain at N-terminal, followed by a proline-rich domain and a transmembrane domain at C-terminal. Quantitative real-time PCR indicated that duMAVS was expressed in all tissues tested across a broad expression spectrum...
2016: Frontiers in Immunology
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