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https://www.readbyqxmd.com/read/28802645/p2x7-purinergic-receptors-participate-in-the-expression-and-extinction-processes-of-contextual-fear-conditioning-memory-in-mice
#1
L B Domingos, S C Hott, A L B Terzian, L B M Resstel
The purinergic system consists of two large receptor families - P2X and P2Y. Both are activated by adenosine triphosphate (ATP), although presenting different functions. These receptors are present in several brain regions, including those involved in emotion and stress-related behaviors. Hence, they seem to participate in fear- and anxiety-related responses. However, few studies have investigated the purinergic system in threatening situations, as observed in contextual fear conditioning (CFC). Therefore, this study investigated the involvement of purinergic receptors in the expression and extinction of aversive memories...
August 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28798231/p2x7-receptor-antagonism-prevents-il-1%C3%AE-release-from-salivary-epithelial-cells-and-reduces-inflammation-in-a-mouse-model-of-autoimmune-exocrinopathy
#2
Mahmoud G Khalafalla, Lucas T Woods, Jean M Camden, Aslam A Khan, Kirsten H Limesand, Michael J Petris, Laurie Erb, Gary A Weisman
Salivary gland inflammation is a hallmark of Sjogrens syndrome (SS), a common autoimmune disease characterized by lymphocytic infiltration of the salivary gland and loss of saliva secretion, predominantly in women. The P2X7 receptor (P2X7R) is an ATP-gated non-selective cation channel that induces inflammatory responses in cells and tissues, including salivary gland epithelium. In immune cells, P2X7R activation induces the production of proinflammatory cytokines, including IL-1β and IL-18, by inducing the oligomerization of the multiprotein complex NLRP3-type inflammasome...
August 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28791020/p2x7-receptor-induces-tumor-necrosis-factor-%C3%AE-converting-enzyme-activation-and-release-to-boost-tnf-%C3%AE-production
#3
Maria Barberà-Cremades, Ana I Gómez, Alberto Baroja-Mazo, Laura Martínez-Alarcón, Carlos M Martínez, Carlos de Torre-Minguela, Pablo Pelegrín
Tumor necrosis factor (TNF)-α is a major pro-inflammatory cytokine produced in response to toll-like receptor stimulation. TNF-α release is controlled by the activity of TNF-α converting enzyme (TACE) that cut membrane-bound TNF-α to shed its ectodomain as a soluble cytokine. The purinergic receptor P2X ligand-gated ion channel 7 (P2X7) is activated in response to elevated concentrations of extracellular ATP and induces different pro-inflammatory pathways in macrophages to establish an inflammatory response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28769008/ketamine-alleviates-depressive-like-behaviors-via-down-regulating-inflammatory-cytokines-induced-by-chronic-restraint-stress-in-mice
#4
Sijie Tan, Yan Wang, Ke Chen, Zhifeng Long, Ju Zou
The purpose of the present study was to investigate whether ketamine's rapid antidepressant effects were associated with its anti-inflammatory actions and to explore the underlying molecular mechanism. Depressive-like behaviors was induced in mice using chronic restraint stress (CRS) method. Anti-depressive effects of ketamine were evaluated by forced swimming tests (FST) and sucrose preference test (SPT). Subsequently, brain tissue was harvested to investigate inflammatory response in the hippocampus via investigating reactive microglia numbers, serum cytokines levels and the toll-like receptor type 4 (TLR4)/p38 mitogen-activated protein kinase (MAPK) pathway...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28762847/inhibition-of-nlrp3-inflammasome-a-new-protective-mechanism-of-cinnamaldehyde-in-endotoxin-poisoning-of-mice
#5
Feng Xu, Feng Wang, Taoqun Wen, Wentao Sang, Dejian Wang, Nan Zeng
CONTEXT: Cinnamaldehyde (CA) has a protective effect in endotoxin poisoning of mice, but there is no direct evidence for the protective effect of CA through inhibition of NLRP3 inflammasome activation in endotoxin poisoning of mice. OBJECTIVE: We aimed to investigate the protective mechanism of CA in endotoxin poisoned mice through NLRP3 inflammasome. MATERIALS AND METHODS: First, we evaluated the anti-inflammatory effect of CA in phorbol-12-myristate acetate-differentiated THP-1 cells through the NLRP3 inflammasome...
August 1, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28757683/chemokines-ccl3-ccl4-and-ccl5-inhibit-atp-induced-release-of-il-1%C3%AE-by-monocytic-cells
#6
Anca-Laura Amati, Anna Zakrzewicz, Kathrin Siebers, Sigrid Wilker, Sarah Heldmann, Dariusz Zakrzewicz, Andreas Hecker, J Michael McIntosh, Winfried Padberg, Veronika Grau
Chemokines and ATP are among the mediators of inflammatory sites that can enter the circulation via damaged blood vessels. The main function of chemokines is leukocyte mobilization, and ATP typically triggers inflammasome assembly. IL-1β, a potent inflammasome-dependent cytokine of innate immunity, is essential for pathogen defense. However, excessive IL-1β may cause life-threatening systemic inflammation. Here, we hypothesize that chemokines control ATP-dependent secretion of monocytic IL-1β. Lipopolysaccharide-primed human monocytic U937 cells were stimulated with the P2X7 agonist BzATP for 30 min to induce IL-1β release...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28747389/neuronal-p2x7-receptor-involvement-in-neuronal-physiology-and-pathology
#7
M Teresa Miras-Portugal, Álvaro Sebastián-Serrano, Laura de Diego García, Miguel Díaz-Hernández
The proposed presence of P2X7 receptor (P2X7R) in neurons has been the source of some contention. Initial studies suggested an absence of P2X7R mRNA in neurons, and the apparent nonspecificity of the antibodies used to identify P2X7R raised further doubts. However, subsequent studies using new pharmacological and biomolecular tools provided conclusive evidence supporting the existence of functional P2X7Rs in neurons. The P2X7 receptor has since been shown to play a leading role in multiple aspects of neuronal physiology, including axonal elongation and branching and neurotransmitter release...
July 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28747388/neuronal-p2x7-receptors-revisited-do-they-really-exist
#8
Peter Illes, Tahir Muhammad Khan, Patrizia Rubini
P2X7 receptors (Rs) constitute a subclass of ATP-sensitive ionotropic receptors (P2X1-P2X7). P2X7Rs have many distinguishing features, mostly based on their long intracellular C terminus regulating trafficking to the cell membrane, protein-protein interactions, and post-translational modification. Their C-terminal tail is especially important in enabling the transition from the nonselective ion channel mode to a membrane pore allowing the passage of large molecules. There is an ongoing dispute on the existence of neuronal P2X7Rs with consequences for our knowledge on their involvement in neuroinflammation, aggravating stroke, temporal lobe epilepsy, neuropathic pain, and various neurodegenerative diseases...
July 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28741143/salidroside-ameliorates-diabetic-neuropathic-pain-in-rats-by-inhibiting-neuroinflammation
#9
Gui-Lian Ni, Rong Cui, Ai-Min Shao, Zhong-Min Wu
More than half of diabetic patients suffer from intractable neuropathic pain. As inflammation plays an important role in diabetic neuropathic pain, anti-inflammatory drugs might have therapeutic potentials for neuropathic pain. Salidroside (SAL), a phenylpropanoid glucoside, modulates a variety of cell functions, including inflammation. Here, we explored anti-nociceptive and anti-inflammatory effects of SAL on Zucker diabetic fatty rats with type 2 diabetes (DM rats). DM rats were tested for mechanical and thermal hyperalgesia using von Frey filament and plantar hot box test, respectively...
July 24, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28740491/nod-like-receptor-p3-inflammasome-controls-protective-th1-th17-immunity-against-pulmonary-paracoccidioidomycosis
#10
Claudia Feriotti, Eliseu Frank de Araújo, Flavio Vieira Loures, Tania Alves da Costa, Nayane Alves de Lima Galdino, Dario Simões Zamboni, Vera Lucia Garcia Calich
The NOD-like receptor P3 (NLRP3) inflammasome is an intracellular multimeric complex that triggers the activation of inflammatory caspases and the maturation of IL-1β and IL-18, important cytokines for the innate immune response against pathogens. The functional NLRP3 inflammasome complex consists of NLRP3, the adaptor protein apoptosis-associated speck-like protein, and caspase-1. Various molecular mechanisms were associated with NLRP3 activation including the presence of extracellular ATP, recognized by the cell surface P2X7 receptor (P2X7R)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28728214/p2x-receptor-channels-in-chronic-pain-pathways
#11
REVIEW
Louis-Philippe Bernier, Ariel R Ase, Philippe Séguéla
Chronic pain is a highly prevalent debilitating condition for which treatment options remain limited for many patients. Ionotropic ATP signaling through excitatory and calcium-permeable P2X receptor-channels is now rightfully considered as a critical player in pathological pain generation and maintenance, therefore their selective targeting represents a therapeutic opportunity with promising yet untapped potential. Recent advances in the structural, functional and pharmacological characterization of rodent and human ATP-gated P2X receptor-channels have shed brighter light on the role of specific subtypes in the pathophysiology of chronic inflammatory, neuropathic or cancer pain...
July 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28725637/opportunistic-pathogen-porphyromonas-gingivalis-modulates-danger-signal-atp-mediated-antibacterial-nox2-pathways-in-primary-epithelial-cells
#12
JoAnn S Roberts, Kalina R Atanasova, Jungnam Lee, Gill Diamond, Jeff Deguzman, Chul Hee Choi, Özlem Yilmaz
Porphyromonas gingivalis, a major opportunistic pathogen in the etiology of chronic periodontitis, successfully survives in human gingival epithelial cells (GECs). P. gingivalis abrogates the effects of a host danger molecule, extracellular ATP (eATP)/P2X7 signaling, such as the generation of reactive oxygen species (ROS) via the mitochondria and NADPH oxidases (NOX) from primary GECs. However, antimicrobial functions of ROS production are thoroughly investigated in myeloid-lineage immune cells and have not been well-understood in epithelial cells...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28723547/the-p2x7-receptor-in-infection-and-inflammation
#13
REVIEW
Francesco Di Virgilio, Diego Dal Ben, Alba Clara Sarti, Anna Lisa Giuliani, Simonetta Falzoni
Adenosine triphosphate (ATP) accumulates at sites of tissue injury and inflammation. Effects of extracellular ATP are mediated by plasma membrane receptors named P2 receptors (P2Rs). The P2R most involved in inflammation and immunity is the P2X7 receptor (P2X7R), expressed by virtually all cells of innate and adaptive immunity. P2X7R mediates NLRP3 inflammasome activation, cytokine and chemokine release, T lymphocyte survival and differentiation, transcription factor activation, and cell death. Ten human P2RX7 gene splice variants and several SNPs that produce complex haplotypes are known...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28716092/the-role-of-microglial-p2x7-modulation-of-cell-death-and-cytokine-release
#14
Yingbo He, Natalie Taylor, Lawrence Fourgeaud, Anindya Bhattacharya
BACKGROUND: ATP-gated P2X7 is a non-selective cation channel, which participates in a wide range of cellular functions as well as pathophysiological processes including neuropathic pain, immune response, and neuroinflammation. Despite its abundant expression in microglia, the role of P2X7 in neuroinflammation still remains unclear. METHODS: Primary microglia were isolated from cortices of P0-2 C57BL/6 wild-type or P2X7 knockout (P2X7(-/-)) mouse pups. Lipopolysaccharide, lipopolysaccharide plus IFNγ, or IL4 plus IL13 were used to polarize microglia to pro-inflammatory or anti-inflammatory states...
July 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28712872/suppression-of-cd36-attenuates-adipogenesis-with-a-reduction-of-p2x7-expression-in-3t3-l1-cells
#15
Huanqing Gao, Danyang Li, Ping Yang, Lei Zhao, Li Wei, Yaxi Chen, Xiong Z Ruan
Adipogenesis is a process of differentiation from preadipocyte into adipocyte, and is regulated by several transcription factors, including the peroxisome proliferator-activated receptor gamma (PPARγ) and the CCAAT-enhancer-binding protein alpha (C/EBPα). CD36 is a membrane protein which contributes to the metabolic disorders such as obesity. Although the previous study demonstrated CD36 participated in the progression of adipogenesis, the mechanism is still unclear. We report here that knockdown of CD36 expression by CD36 small interfering RNA (siRNA) resulted in a reduction of adipocyte differentiation and adipogenic protein expression...
July 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28707031/silencing-of-p2x7r-by-rna-interference-in-the-hippocampus-can-attenuate-morphological-and-behavioral-impact-of-pilocarpine-induced-epilepsy
#16
Rebeca Padrão Amorim, Michelle Gasparetti Leão Araújo, Jorge Valero, Iscia Lopes-Cendes, Vinicius Davila Bitencourt Pascoal, João Oliveira Malva, Maria José da Silva Fernandes
Cell signaling mediated by P2X7 receptors (P2X7R) has been suggested to be involved in epileptogenesis, via modulation of intracellular calcium levels, excitotoxicity, activation of inflammatory cascades, and cell death, among other mechanisms. These processes have been described to be involved in pilocarpine-induced status epilepticus (SE) and contribute to hyperexcitability, resulting in spontaneous and recurrent seizures. Here, we aimed to investigate the role of P2X7R in epileptogenesis in vivo using RNA interference (RNAi) to inhibit the expression of this receptor...
July 13, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28702712/evaluation-of-the-anticonvulsant-effect-of-brilliant-blue-g-a-selective-p2x7-receptor-antagonist-in%C3%A2-the-iv-ptz-maximal-electroshock-and-6%C3%A2-hz-induced-seizure-tests-in-mice
#17
Dorota Nieoczym, Katarzyna Socała, Piotr Wlaź
Epilepsy is one of the most common neurological disorders which is diagnosed in around 65 million people worldwide. Clinically available antiepileptic drugs fail to control epileptic activity in about 30% of patients and they are merely symptomatic treatments and cannot cure or prevent epilepsy. There remains a need for searching new therapeutic strategies for epileptic disorders. The P2X7 receptor has been recently investigated as a new target in epilepsy treatment. Preclinical studies revealed that P2X7 receptor antagonists have anticonvulsant properties in some models of epilepsy...
July 12, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28694030/antimicrobial-peptide-gold-nanoscale-therapeutic-formulation-with-high-skin-regenerative-potential
#18
Michela Comune, Akhilesh Rai, Kiran K Chereddy, Sandra Pinto, Sezin Aday, André F Ferreira, Alessandra Zonari, Josephine Blersch, Rodrigo Cunha, Ricardo Rodrigues, Juan Lerma, Pedro N Simões, Veronique Préat, Lino Ferreira
Chronic skin wounds affect ≈3% of persons aged >60years (Davies et al., 2007) [1]. These wounds are typically difficult to heal by conventional therapies and in many cases they get infected making even harder the regeneration process. The antimicrobial peptide (AMP) LL37 combines antimicrobial with pro-regenerative properties and thus represents a promising topical therapy to address both problems. Here, we investigated the wound healing potential of soluble and immobilized LL37 (LL37-conjugated gold nanoparticles, LL37-Au NPs), both in vitro (migration of keratinocytes) and in vivo (skin wound healing)...
July 8, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28687781/p2x7-receptor-antagonism-modulates-il-1%C3%AE-and-mmp9-in-human-atherosclerotic-vessels
#19
Maria Lombardi, Maria Elena Mantione, Domenico Baccellieri, David Ferrara, Renata Castellano, Roberto Chiesa, Ottavio Alfieri, Chiara Foglieni
In atherosclerosis, matrix metallopeptidases (MMPs) contribute to plaque rupture through weakening of the fibrous cap. Pleiotropic P2X purinoceptor 7 (P2X7), expressed in the carotid plaque (PL), is involved in interleukin 1 beta (IL-1β) release that may influence MMP9 generation, thus their possible modulation through acting on P2X7 was investigated. P2X7-related machinery was characterized and the effects of P2X7 antagonists (A740003, KN62) and MMPs inhibitors (Batimastat, Ro28-2653) were studied in ex-vivo tissue cultures of human PL's vs...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687662/virus-triggered-atp-release-limits-viral-replication-through-facilitating-ifn-%C3%AE-production-in-a-p2x7-dependent-manner
#20
Chengfei Zhang, Hongwang He, Li Wang, Na Zhang, Hongjun Huang, Qingqing Xiong, Yan Yan, Nannan Wu, Hua Ren, Honghui Han, Mingyao Liu, Min Qian, Bing Du
Accumulating evidence shows that innate immune responses are associated with extracellular nucleotides, particularly ATP. In this article, we demonstrate extensive protection of ATP/P2X7 signaling in a host against viral infection. Interestingly, we observed a significant increase in ATP as a danger signal in vesicular stomatitis virus (VSV)-infected cell supernatant and VSV-infected mice in an exocytosis- and pannexin channel-dependent manner. Furthermore, extracellular ATP reduces the replication of VSV, Newcastle disease virus, murine leukemia virus, and HSV in vivo and in vitro through the P2X7 receptor...
July 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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