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Gergely Kovács, Zsuzsanna Környei, Krisztina Tóth, Mária Baranyi, János Brunner, Máté Neubrandt, Ádám Dénes, Beáta Sperlágh
The P2X7R protein, a P2 type purinergic receptor functioning as a non-selective cation channel, is expressed in different cell types of the central nervous system in several regions of the brain. The activation of the P2X7R protein by ATP modulates excitatory neurotransmission and contributes to microglial activation, apoptosis and neuron-glia communication. Zinc is an essential micronutrient that is highly concentrated in the synaptic vesicles of glutamatergic hippocampal neurons where free zinc ions released into the synaptic cleft alter glutamatergic signal transmission...
July 30, 2018: Cell Calcium
Ben J Gu, James S Wiley
The P2X7 receptor (P2X7 or P2X7R) has been widely studied for ATP-induced proinflammation, but in the absence of ligand, P2X7 has a second function as a scavenger receptor which is active in the development of human brain. The scavenger activity of P2X7 is only evident in the absence of serum but is fully active in cerebrospinal fluid. P2X7 on the cell surface is present as a membrane complex and an attachment to nonmuscle myosin of the cytoskeleton is required for particle engulfment. Selective antagonists of P2X7 proinflammatory function have little effect on phagocytosis but coinheritance of a haplotype spanning in P2RX7 and P2RX4 genes has been associated with loss of P2X7 mediated phagocytosis...
August 10, 2018: British Journal of Pharmacology
Sanja Cicko, Thomas Christian Köhler, Cemil Korcan Ayata, Tobias Müller, Nicolas Ehrat, Anja Meyer, Madelon Hossfeld, Andreas Zech, Francesco Di Virgilio, Marco Idzko
Acute respiratory distress syndrome (ARDS) is a life-threating lung condition resulting from a direct and indirect injury to the lungs [1, 2]. Pathophysiologically it is characterized by an acute alveolar damage, an increased permeability of the microvascular-barrier, leading to protein-rich pulmonary edema and subsequent impairment of arterial oxygenation and respiratory failure [1]. This study examined the role of extracellular ATP in recruiting inflammatory cells to the lung after induction of acute lung injury with lipopolysaccharide (LPS)...
July 17, 2018: Oncotarget
Jan M Deussing, Eduardo Arzt
Depression is a prime contributor to global disease burden with 300 million affected patients worldwide. The persistent lack of progress with regards to pharmacotherapy stands in stark contrast to the pandemic magnitude of the disease. Alterations of inflammatory pathways in depressed patients, including altered circulating pro-inflammatory cytokines, have been put forward as a potential pathophysiological mechanism. The P2X7 receptor (P2X7R) plays an important role regulating the release of interleukin-1β and other cytokines...
August 6, 2018: Trends in Molecular Medicine
Tomasz Grygorowicz, Beata Dąbrowska-Bouta, Lidia Strużyńska
Purinergic P2X receptors, when activated under pathological conditions, participate in induction of the inflammatory response and/or cell death. Both neuroinflammation and neurodegeneration represent hallmarks of multiple sclerosis (MS), an autoimmune disease of the central nervous system. In the current study, we examined whether P2X7R is expressed in brain microvasculature of rats subjected to experimental autoimmune encephalomyelitis (EAE) and explore possible relationships with blood-brain barrier (BBB) protein-claudin-5 after administration of P2X7R antagonist-Brilliant Blue G (BBG)...
August 8, 2018: Purinergic Signalling
Sara Tezza, Moufida Ben Nasr, Francesca D'Addio, Andrea Vergani, Vera Usuelli, Simonetta Falzoni, Roberto Bassi, Sergio Dellepiane, Carmen Fotino, Chiara Rossi, Anna Maestroni, Anna Solini, Domenico Corradi, Elisa Giani, Chiara Mameli, Federico Bertuzzi, Marcus Guy Pezzolesi, Clive H Wasserfall, Mark A Atkinson, Ernst-Martin Füchtbauer, Camillo Ricordi, Franco Folli, Francesco Di Virgilio, Antonello Pileggi, Sirano Dhe-Paganon, Gian Vincenzo Zuccotti, Paolo Fiorina
Extracellular ATP (eATP) activates T cells by engaging the P2X7R receptor. We identified two loss-of-function P2X7R mutations that are protective against type 1 diabetes (T1D) and thus hypothesized that eATP/P2X7R signaling may represent an early step in T1D onset. Specifically, we observed that in newly diagnosed T1D patients, P2X7R is upregulated on CD8+ effector T cells in comparison to healthy controls. eATP is released at high levels by human/murine islets in vitro in high-glucose/inflammatory conditions, thus upregulating P2X7R on CD8+ T cells in vitro P2X7R blockade with oxidized ATP (oATP) reduces the CD8+ T cell-mediated autoimmune response in vitro and delays diabetes onset in NOD mice...
July 31, 2018: Diabetes
Lu Lin, Shanjun Huang, Zhouyang Zhu, Jibo Han, Zhengxian Wang, Weijian Huang, Zhouqing Huang
The rupture of atherosclerotic plaques may result in the formation of thrombi, which may induce subsequent cardiac events such as acute myocardial infarction. Overproduction of matrix metalloproteinases (MMPs) and extracellular matrix metalloproteinase inducers (EMMPRINs) by monocytes and macrophages may lead to rupture of atherosclerotic plaques as a result of the degradation of the extracellular matrix. The purinergic 2X7 receptor (P2X7R) is expressed in macrophages that are assembled in atherosclerotic lesions of human carotid arteries...
September 2018: Molecular Medicine Reports
Rai Khalid Farooq, Arnaud Tanti, Samia Ainouche, Sébastien Roger, Catherine Belzung, Vincent Camus
A polymorphism in the P2RX7 gene that encodes for the P2X7 ionotropic ATP-gated receptor (P2X7R) protein has been shown to be associated with an increased risk for developing depressive illnesses. However, the role of P2X7R in depression is still unclear. To better understand the role of P2X7R and its subsequent impact on microglial activation, we compared the effect of the P2X7R antagonist Brilliant Blue G (BBG) with that of fluoxetine in an unpredictable chronic mild stress (UCMS) model of depression in mice...
July 10, 2018: Psychoneuroendocrinology
Francesca D'Addio, Andrea Vergani, Luciano Potena, Anna Maestroni, Vera Usuelli, Moufida Ben Nasr, Roberto Bassi, Sara Tezza, Sergio Dellepiane, Basset El Essawy, Maria Iascone, Attilio Iacovoni, Laura Borgese, Kaifeng Liu, Gary Visner, Sirano Dhe-Paganon, Domenico Corradi, Reza Abdi, Randall C Starling, Franco Folli, Gian Vincenzo Zuccotti, Mohamed H Sayegh, Peter S Heeger, Anil Chandraker, Francesco Grigioni, Paolo Fiorina
Purinergic receptor-7 (P2X7R) signaling controls Th17 and Th1 generation/differentiation, while NOD-like receptor P3 (NLRP3) acts as a Th2 transcriptional factor. Here, we demonstrated the existence of a P2X7R/NLRP3 pathway in T cells that is dysregulated by a P2X7R intracellular region loss-of-function mutation, leading to NLRP3 displacement and to excessive Th17 generation due to abrogation of the NLRP3-mediated Th2 program. This ultimately resulted in poor outcomes in cardiac-transplanted patients carrying the mutant allele, who showed abnormal Th17 generation...
August 1, 2018: Journal of Clinical Investigation
Francesco Di Virgilio, Alba Clara Sarti, Simonetta Falzoni, Elena De Marchi, Elena Adinolfi
Modulation of the biochemical composition of the tumour microenvironment is a new frontier of cancer therapy. Several immunosuppressive mechanisms operate in the milieu of most tumours, a condition that makes antitumour immunity ineffective. One of the most potent immunosuppressive factors is adenosine, which is generated in the tumour microenvironment owing to degradation of extracellular ATP. Accruing evidence over the past few years shows that ATP is one of the major biochemical constituents of the tumour microenvironment, where it acts at P2 purinergic receptors expressed on both tumour and host cells...
July 13, 2018: Nature Reviews. Cancer
A Chaudhary, J P Singh, P K Sehajpal, B C Sarin
BACKGROUND: Genetic elements are known to influence susceptibility to tuberculosis (TB). P2X7R is a candidate gene with multiple single-nucleotide polymorphisms (SNPs) that has the potential to influence an individual's ability to kill the intracellular pathogen Mycobacterium tuberculosis. OBJECTIVE: To explore the role of five functional polymorphisms of P2X7R in susceptibility or resistance to TB in a North Indian Punjabi population. DESIGN: A case-control study was conducted among 245 TB patients (145 pulmonary TB [PTB] and 100 extra-pulmonary TB [EPTB]) and 247 healthy controls...
August 1, 2018: International Journal of Tuberculosis and Lung Disease
Preetha Shridas, Maria C De Beer, Nancy R Webb
Serum amyloid A (SAA) is a high-density apolipoprotein whose plasma levels can increase more than 1000-fold during a severe acute-phase inflammatory response and are more modestly elevated in chronic inflammation. SAA is thought to play important roles in innate immunity, but its biological activities have not been completely delineated. We previously reported that SAA deficiency protects mice from developing abdominal aortic aneurysms (AAAs) induced by chronic angiotensin II (AngII) infusion. Here, we report that SAA is required for AngII-induced increases in interleukin-1 beta (IL-1β), a potent proinflammatory cytokine that is tightly controlled by the Nod-like receptor protein 3 (NLRP3) inflammasome and caspase-1 and has been implicated in both human and mouse AAAs...
July 5, 2018: Journal of Biological Chemistry
Zeynep Seref-Ferlengez, Marcia Urban-Maldonado, Hui B Sun, Mitchell B Schaffler, Sylvia O Suadicani, Mia M Thi
The pannexin 1 (Panx1) channel is a mechanosensitive channel that interacts with P2X7 receptors (P2X7R) to form a functional complex that has been shown in vitro to play an essential role in osteocyte mechanosignaling. While the participation of P2X7R in skeletal responses to mechanical loading has been demonstrated, the role of Panx1 and its interplay with P2X7R still remain to be determined. In this study, we use a global Panx1-/- mouse model and in vivo mechanical loading to demonstrate that Panx1 channels play an essential role in load-induced skeletal responses...
June 28, 2018: Annals of the New York Academy of Sciences
Anja Pfalzgraff, Sergio Bárcena-Varela, Lena Heinbockel, Thomas Gutsmann, Klaus Brandenburg, Guillermo Martinez-de-Tejada, Günther Weindl
BACKGROUND AND PURPOSE: Wound healing is a complex process that is essential to provide skin homeostasis. Infection with pathogenic bacteria such as Staphylococcus aureus can lead to chronic wounds, which are challenging to heal. Previously, we demonstrated that the antimicrobial endotoxin-neutralizing peptide Pep19-2.5 promotes artificial wound closure in keratinocytes. Here, we investigated the mechanism of peptide-induced cell migration and if Pep19-2.5 accelerates wound closure in vivo...
June 26, 2018: British Journal of Pharmacology
Elodie Martin, Majid Amar, Carine Dalle, Ihsen Youssef, Céline Boucher, Caroline Le Duigou, Matthias Brückner, Annick Prigent, Véronique Sazdovitch, Annett Halle, Jean M Kanellopoulos, Bertrand Fontaine, Benoît Delatour, Cécile Delarasse
Extracellular aggregates of amyloid β (Aβ) peptides, which are characteristic of Alzheimer's disease (AD), act as an essential trigger for glial cell activation and the release of ATP, leading to the stimulation of purinergic receptors, especially the P2X7 receptor (P2X7R). However, the involvement of P2X7R in the development of AD is still ill-defined regarding the dual properties of this receptor. Particularly, P2X7R activates the NLRP3 inflammasome leading to the release of the pro-inflammatory cytokine, IL-1β; however, P2X7R also induces cleavage of the amyloid precursor protein generating Aβ peptides or the neuroprotective fragment sAPPα...
June 22, 2018: Molecular Psychiatry
Xin Han, Jian Song, Li-Hua Lian, You-Li Yao, Dan-Yang Shao, Ying Fan, Li-Shuang Hou, Ge Wang, Shuang Zheng, Yan-Ling Wu, Ji-Xing Nan
Ginseng is widely used in energy drinks, dietary supplements, and herbal medicines, and its pharmacological actions are related with energy metabolism. As an important modulating energy metabolism pathway, liver X receptors (LXRs) can promote the resolving of hepatic fibrosis and inflammation. The present study aims to evaluate the regulation of 25-OCH3 -PPD, a ginsenoside isolated from Panax ginseng, against hepatic fibrosis and inflammation in thioacetamide (TAA)-stimulated mice by activating the LXRs pathway...
July 11, 2018: Journal of Agricultural and Food Chemistry
Xinhua Yin
No abstract text is available yet for this article.
June 2018: Journal of Cellular and Molecular Medicine
Julieta E Ochoa-Amaya, Nicolle Queiroz-Hazarbassanov, Lilian B Namazu, Atilio S Calefi, Carla N Tobaruela, Rafael Margatho, João Palermo-Neto, Ana P Ligeiro de Oliveira, Luciano F Felicio
PURPOSE: We have previously shown that domperidone-induced short-term hyperprolactinemia reduces the lung's allergic inflammatory response in an ovalbumin antigenic challenge model. Since purinergic receptor P2X7R activity leads to proinflammatory cytokine release and is possibly related to the pathogenesis of allergic respiratory conditions, the present study was designed to investigate a possible involvement of purinergic and prolactin receptors in this phenomenon. METHODS: To induce hyperprolactinemia, domperidone was injected intraperitoneally in rats at a dose of 5...
June 6, 2018: Neuroimmunomodulation
Julio A Diaz-Perez, Meaghan E Killeen, Yin Yang, Cara D Carey, Louis D Falo, Alicia R Mathers
Psoriasis is a chronic inflammatory skin disease dependent on the IL-23/IL-17 axis, a potent inflammatory pathway involved in pathogen clearance and autoimmunity. Several triggers have been proposed as initiators for psoriasis, including alarmins such as ATP. However, the role of alarmins in psoriasis pathogenesis and cutaneous inflammation has not been well addressed. Herein studies demonstrate that signaling through the P2X7 receptor (P2X7R) pathway underlies the development of psoriasiform inflammation. In this regard, psoriasiform dermatitis induced by IL-23 is dependent on P2X7R signaling...
June 2, 2018: Journal of Investigative Dermatology
Catherine A Christian
No abstract text is available yet for this article.
January 2018: Epilepsy Currents
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