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https://www.readbyqxmd.com/read/28101847/off-target-anti-inflammatory-activity-of-the-p2x7-receptor-antagonist-az11645373
#1
Olga V Oskolkova, Viktoria Godschachner, Valery N Bochkov
We have found that a well-characterized P2X7 receptor antagonist AZ11645373 blocked production of pro-inflammatory chemokine IL-8 in endothelial cells treated with OxPAPC. The effect was not due to toxicity of AZ11645373 as documented by cellular metabolic activity assay. The mechanism of inhibition by AZ11645373 was apparently independent of the P2X7 receptor because this receptor was not involved in induction of IL-8 under our experimental conditions. In support of this notion, two P2X7 agonists ATP and BzATP did not upregulate IL-8...
January 19, 2017: Inflammation
https://www.readbyqxmd.com/read/28089560/critical-role-of-p2x7-receptors-in-the-neuroinflammation-and-cognitive-dysfunction-after-surgery
#2
Bin Zheng, Renchun Lai, Jun Li, Zhiyi Zuo
Postoperative cognitive dysfunction worsens patient outcome after surgery. Neuroinflammation is a critical neuropathological process for it. We determined the role of P2X7 receptors, proteins that participate in inflammatory response, in the neuroinflammation induction after surgery, and whether the choice of volatile anesthetics affects its occurrence. Eight-week old C57BL/6J or P2X7 receptor knockout male mice were subjected to right carotid arterial exposure under anesthesia with 1.8% isoflurane, 2.5% sevoflurane or 10% desflurane...
January 9, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28069296/inflammatory-early-events-associated-to-the-role-of-p2x7-receptor-in-acute-murine-toxoplasmosis
#3
Gladys Corrêa, Carolina de Almeida Lindenberg, Aline Cristina de Abreu Moreira-Souza, Luiz Eduardo Baggio Savio, Christina Maeda Takiya, Camila Marques-da-Silva, Rossiane Claudia Vommaro, Robson Coutinho-Silva
Activation of the purinergic P2X7 receptor by extracellular ATP (eATP) potentiates proinflammatory responses during infections by intracellular pathogens. Extracellular ATP triggers an antimicrobial response in macrophages infected with Toxoplasma gondii in vitro, suggesting that purinergic signaling may stimulate host defense mechanisms against toxoplasmosis. Here, we provide in vivo evidence in support of this hypothesis, by showing that P2X7(-/-) mice are more susceptible than P2X7(+/+) mice to acute infection by the RH strain of T...
December 30, 2016: Immunobiology
https://www.readbyqxmd.com/read/28063215/hypoxia-independent-mechanisms-of-hif-1%C3%AE-expression-in-astrocytes-after-ischemic-preconditioning
#4
Yuri Hirayama, Schuichi Koizumi
We recently demonstrated that ischemic tolerance was dependent on astrocytes, for which HIF-1α had an essential role. The mild ischemia (preconditioning; PC) increased HIF-1α in a biphasic pattern, that is, a quick and transient increase in neurons, followed by a slow and sustained increase in astrocytes. However, mechanisms underlying such temporal difference in HIF-1α increase remain totally unknown. Here, we show that unlike a hypoxia-dependent mechanism in neurons, astrocytes increase HIF-1α via a novel hypoxia-independent but P2X7-dependent mechanism...
January 7, 2017: Glia
https://www.readbyqxmd.com/read/28062289/evaluation-of-p2x7-receptor-expression-in-peripheral-lymphocytes-and-immune-profile-from-patients-with-indeterminate-form-of-chagas-disease
#5
Viviane do Carmo Gonçalves Souza, Joabel Tonellotto Dos Santos, Fernanda Licker Cabral, Fernanda Barbisan, Maria Isabel Azevedo, Luiz Felipe Dias Carli, Sonia de Avila Botton, Jeandre Augusto Dos Santos Jaques, Daniela Bitencourt Rosa Leal
Chagas disease (CD) is caused by Trypanosoma cruzi, an intracellular protozoan which is a potent stimulator of cell-mediated immunity. In the indeterminate form of CD (IFCD) a modulation between pro- and anti-inflammatory responses establishes a host-parasite adaptation. It was previously demonstrated that purinergic ecto-enzymes regulates extracellular ATP and adenosine levels, influencing immune and inflammatory processes during IFCD. In inflammatory sites ATP, as well as its degradation product, adenosine, function as signaling molecules and immunoregulators through the activation of purinergic receptors...
January 3, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28061416/purinergic-p2x7-receptor-mediates-acetaldehyde-induced-hepatic-stellate-cells-activation-via-pkc-dependent-gsk3%C3%AE-pathway
#6
Xiaojuan Wu, Yuhui Wang, Sheng Wang, Rixiang Xu, Xiongwen Lv
The activation of hepatic stellate cells (HSCs) is an essential part in the development of alcoholic liver fibrosis (ALF). In this study, stimulated HSCs with 200μM acetaldehyde for 48h was used to imitate alcoholic liver fibrosis in vitro. The western blot and qRT-PCR results showed that P2X7R expression was significantly increased in the activation of HSCs after acetaldehyde treatment. Interestingly, activation of P2X7R by stimulating with P2X7R agonist BzATP significantly promoted acetaldehyde-induced CyclinD1 expression, cell proportion in S phase, inflammatory response, and the protein and mRNA levels of α-SMA, collagen I...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28051090/retinoic-acid-takes-effector-t-cells-to-the-gallows-p2x7-the-molecular-hangman
#7
S Das, E J Villablanca
Effector T-cell contraction is one of the primary means by which immune homeostasis in the peripheral tissues is reestablished following an inflammatory response. In this issue of Mucosal Immunology, Hashimoto-Hill et al.(1) show that retinoic acid (RA) transcriptionally upregulates P2X7 primarily in effector T cells of the intestine sensitizing them to NAD-induced cell death (NICD); thus, demonstrating a previously unrecognized role of RA in effector T-cell contraction.Mucosal Immunology advance online publication, 4 January 2017; doi:10...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28039938/targeted-p2x7-r-shrna-delivery-attenuates-sympathetic-nerve-sprouting-and-ameliorates-cardiac-dysfunction-in-rats-with-myocardial-infarction
#8
Hongmei Gao, Jie Yin, Yugen Shi, Hesheng Hu, Xiaolu Li, Mei Xue, Wenjuan Cheng, Ye Wang, Xinran Li, Yongkang Li, Yu Wang, Suhua Yan
BACKGROUND: Inflammation-dominated sympathetic sprouting adjacent to the necrotic region following myocardial infarction (MI) has been implicated in the etiology of arrhythmias resulting in sudden cardiac death; however, the mechanisms responsible remain to be elucidated. Although P2X7 R is a key immune mediator, its role has yet to be explored. OBJECTIVE: We investigated whether P2X7 R regulates NF-κB and affects cardiac sympathetic reinnervation in rats undergoing MI...
December 31, 2016: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28039004/localized-inhibition-of-p2x7r-at-the-spinal-cord-injury-site-improves-neurogenic-bladder-dysfunction-by-decreasing-urothelial-p2x3r-expression-in-rats
#9
Alvaro Munoz, Iman K Yazdi, Xiufeng Tang, Carolina Rivera, Nima Taghipour, Robert G Grossman, Timothy B Boone, Ennio Tasciotti
AIMS: Reestablishment of bladder function in patients with spinal cord injury (SCI) is a clinical priority. Our objectives were to determine whether SCI-localized inhibition of purinergic P2X7 receptors (P2X7R) improve bladder function by decreasing afferent signals mediated by urothelial P2X3R. MAIN METHODS: Systemic inhibition of P2X7R may improve locomotion in rodent SCI models; however, beneficial effects on bladder function and its physiological mechanisms have not been evaluated...
December 27, 2016: Life Sciences
https://www.readbyqxmd.com/read/28035410/inhibiting-purinergic-p2x7-receptors-with-the-antagonist-brilliant-blue-g-is-neuroprotective-in-an-intranigral-lipopolysaccharide-animal-model-of-parkinson-s-disease
#10
Xin-Hong Wang, Xin Xie, Xiao-Guang Luo, Hong Shang, Zhi-Yi He
Parkinson's disease (PD) is a common neurodegenerative disorder, which is characterized by the selective and progressive death of dopaminergic (DA) neurons in the substantia nigra. Increasing evidence suggests that inflammation is important in the degeneration of DA neurons. The purinergic receptor subtype P2X7 receptor (P2X7R) is key in the activation and proliferation of microglia. The present study aimed to examine whether inhibiting purinergic P2X7 receptors is neuroprotective in a rat model of PD, specifically via inhibiting p38 mitogen‑activated protein kinase (MAPK)...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28031477/lipin-2-regulates-nlrp3-inflammasome-by-affecting-p2x7-receptor-activation
#11
Gema Lordén, Itziar Sanjuán-García, Nagore de Pablo, Clara Meana, Inés Alvarez-Miguel, M Teresa Pérez-García, Pablo Pelegrín, Jesús Balsinde, María A Balboa
Mutations in human LPIN2 produce a disease known as Majeed syndrome, the clinical manifestations of which are ameliorated by strategies that block IL-1β or its receptor. However the role of lipin-2 during IL-1β production remains elusive. We show here that lipin-2 controls excessive IL-1β formation in primary human and mouse macrophages by several mechanisms, including activation of the inflammasome NLRP3. Lipin-2 regulates MAPK activation, which mediates synthesis of pro-IL-1β during inflammasome priming...
December 28, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28028627/effect-of-electroacupuncture-on-the-cervicospinal-p2x7-receptor-fractalkine-cx3cr1-signaling-pathway-in-a-rat-neck-incision-pain-model
#12
Y H Gao, C W Li, J Y Wang, L H Tan, C L Duanmu, X H Jing, X R Chang, J L Liu
Increasing evidence supports that acupuncture intervention is an effective approach for intraoperative and postoperative pain. Neuron-microglia crosstalk, mediated by the purinergic P2X7 receptor (R)/fractalkine/CX3CR1 cascade in the spinal cord dorsal horn, plays a pivotal role in pain processing. However, its involvement in the analgesic effect of electroacupuncture (EA) remains unclear. In this study, a rat neck-incision pain model was established by making a longitudinal incision along the midline of the neck and subsequent repeated mechanical stimulation...
December 27, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/28027922/the-protective-effect-of-resveratrol-in-the-transmission-of-neuropathic-pain-mediated-by-the-p2x7-receptor-in-the-dorsal-root-ganglia
#13
Jinyan Xie, Shuangmei Liu, Bing Wu, Guilin Li, Shenqiang Rao, Lifang Zou, Zhihua Yi, Chunping Zhang, Tianyu Jia, Shanhong Zhao, Günther Schmalzing, Ralf Hausmann, Hong Nie, Guodong Li, Shangdong Liang
The P2X7 receptor mediates afferent nerve activation and is related to chronic neuropathic pain. Resveratrol (RES) has also been reported to exhibit anti-inflammatory effects. In this study, we investigated the neuroprotective effect of RES on the transmission of neuropathic pain mediated by the P2X7 receptor. The P2X7 mRNA and protein expression levels in L4-L5 dorsal root ganglia (DRG)s of the chronic constriction injury (CCI) group were significantly higher than those observed in the Ctrl + NS, Sham + RES and Sham groups...
December 24, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/28025718/conformational-changes-during-human-p2x7-receptor-activation-examined-by-structural-modelling-and-cysteine-based-cross-linking-studies
#14
Emily A Caseley, Stephen P Muench, Lin-Hua Jiang
The P2X7 receptor (P2X7R) is important in mediating a range of physiological functions and pathologies associated with tissue damage and inflammation and represents an attractive therapeutic target. However, in terms of their structure-function relationships, the mammalian P2X7Rs remain poorly characterised compared to some of their other P2XR counterparts. In this study, combining cysteine-based cross-linking and whole-cell patch-clamp recording, we examined six pairs of residues (A44/I331, D48/I331, I58/F311, S60/L320, I75/P177 and K81/V304) located in different parts of the extracellular and transmembrane domains of the human P2X7R...
December 26, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27999370/effect-of-lead-pb-on-inflammatory-processes-in-the-brain
#15
REVIEW
Karina Chibowska, Irena Baranowska-Bosiacka, Anna Falkowska, Izabela Gutowska, Marta Goschorska, Dariusz Chlubek
That the nervous system is the main target of lead (Pb) has long been considered an established fact until recent evidence has linked the Pb effect on the immune system to the toxic effects of Pb on the nervous system. In this paper, we present recent literature reports on the effect of Pb on the inflammatory processes in the brain, particularly the expression of selected cytokines in the brain (interleukin 6, TGF-β1, interleukin 16, interleukin 18, and interleukin 10); expression and activity of enzymes participating in the inflammatory processes, such as cyclooxygenase 2, caspase 1, nitrogen oxide synthase (NOS 2) and proteases (carboxypeptidases, metalloproteinases and chymotrypsin); and the expression of purine receptors P2X4 and P2X7...
December 19, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27988461/divergent-regulatory-roles-of-extracellular-atp-in-the-degranulation-response-of-mouse-bone-marrow-derived-mast-cells
#16
Kazuki Yoshida, Masaaki Ito, Isao Matsuoka
Mast cells (MCs) play a critical role in allergic inflammation. Although purinergic signalling is implicated in the regulation of various immune responses, its role in MC function is not fully understood. In this study, we investigated the regulatory role of purinergic signalling in MC degranulation, using mouse bone marrow-derived mast cells (BMMCs). Notably, BMMCs expressed various functional P2 adenosine triphosphate (ATP) receptors, including ionotropic P2X4 and P2X7, involved in the regulation of BMMC degranulation...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27976523/neonatal-maternal-deprivation-enhances-presynaptic-p2x7-receptor-transmission-in-insular-cortex-in-an-adult-rat-model-of-visceral-hypersensitivity
#17
Ping-An Zhang, Qiya Xu, Lu Xue, Hang Zheng, Jun Yan, Ying Xiao, Guang-Yin Xu
AIMS: Insular cortex (IC) is involved in processing the information of pain. The aim of this study was to investigate roles and mechanisms of P2X7 receptors (P2X7Rs) in IC in development of visceral hypersensitivity of adult rats with neonatal maternal deprivation (NMD). METHODS: Visceral hypersensitivity was quantified by abdominal withdrawal reflex threshold to colorectal distension (CRD). Expression of P2X7Rs was determined by qPCR and Western blot. Synaptic transmission in IC was recorded by patch-clamp recording...
December 15, 2016: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/27975425/exploration-of-the-p2x7-receptor-pathway-involvement-in-the-anti-inflammatory-activity-of-medicinal-plants-from-the-european-traditional-medicine-through-metabolomics-approach
#18
J Zikovic, G Genta-Jouve, F Massicot, P Rat, B Deguin, D Godevac, N Menkovic, K Savikin, G Zdunic, S Boutefnouchet
No abstract text is available yet for this article.
December 2016: Planta Medica
https://www.readbyqxmd.com/read/27966552/contraction-of-intestinal-effector-t-cells-by-retinoic-acid-induced-purinergic-receptor-p2x7
#19
S Hashimoto-Hill, L Friesen, M Kim, C H Kim
The intestinal environment harbors a large number of activated T cells, which are potentially inflammatory. To prevent inflammatory responses, intestinal T cells are controlled by various tolerogenic mechanisms, including T-cell apoptosis. We investigated the expression mechanism and function of the purinergic receptor P2X7 in contraction of intestinal CD4(+) effector T cells. We found that P2X7 upregulation on CD4(+) effector T cells is induced by retinoic acid through retinoic acid receptor α binding to an intragenic enhancer region of the P2rx7 gene...
December 14, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27965148/an-in-vitro-skin-sensitization-assay-termed-episensa-for-broad-sets-of-chemicals-including-lipophilic-chemicals-and-pre-pro-haptens
#20
Kazutoshi Saito, Osamu Takenouchi, Yuko Nukada, Masaaki Miyazawa, Hitoshi Sakaguchi
To evaluate chemicals (e.g. lipophilic chemicals, pre/pro-haptens) that are difficult to correctly evaluate using in vitro skin sensitization tests (e.g. DPRA, KeratinoSens or h-CLAT), we developed a novel in vitro test termed "Epidermal Sensitization Assay: EpiSensA" that uses reconstructed human epidermis. This assay is based on the induction of multiple marker genes (ATF3, IL-8, DNAJB4 and GCLM) related to two keratinocyte responses (inflammatory or cytoprotective) in the induction of skin sensitization...
December 10, 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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