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https://www.readbyqxmd.com/read/27924062/chenodeoxycholic-acid-activates-nlrp3-inflammasome-and-contributes-to-cholestatic-liver-fibrosis
#1
Zizhen Gong, Jiefei Zhou, Shengnan Zhao, Chunyan Tian, Panliang Wang, Congfeng Xu, Yingwei Chen, Wei Cai, Jin Wu
Accumulation of hydrophobic bile acids in the liver contributes to cholestatic liver injury. Inflammation induced by excessive bile acids is believed to play a crucial role, however, the mechanisms of bile acids triggered inflammatory response remain unclear. Recent studies have highlighted the effect of NLRP3 inflammasome in mediating liver inflammation and fibrosis. In this study, we for the first time showed that chenodeoxycholic acid (CDCA), the major hydrophobic primary bile acid involved in cholestatic liver injury, could dose-dependently induce NLRP3 inflammasome activation and secretion of pro-inflammatory cytokine-IL-1β in macrophages by promoting ROS production and K+ efflux...
December 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27915186/role-of-the-purinergic-signaling-in-epilepsy
#2
REVIEW
Marek Cieślak, Andrzej Wojtczak, Michał Komoszyński
Adenine nucleotides and adenosine are signaling molecules that activate purinergic receptors P1 and P2. Activation of A1 adenosine receptors has an anticonvulsant action, whereas activation of A2A receptors might initiate seizures. Therefore, a significant limitation to the use of A1 receptor agonists as drugs in the CNS might be their peripheral side effects. The anti-epileptic activity of adenosine is related to its increased concentration outside the cell. This increase might result from the inhibition of the equilibrative nucleoside transporters (ENTs)...
September 22, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27893093/ligation-of-cd40-in-human-m%C3%A3-ller-cells-induces-p2x7-receptor-dependent-death-of-retinal-endothelial-cells
#3
Jose-Andres C Portillo, Yalitza Lopez Corcino, George R Dubyak, Timothy S Kern, Shigemi Matsuyama, Carlos S Subauste
Purpose: Cluster of differentiation 40 (CD40) is required for retinal capillary degeneration in diabetic mice, a process mediated by the retinal endothelial cells (REC) death. However, CD40 activates prosurvival signals in endothelial cells. The purpose of this study was to identify a mechanism by which CD40 triggers programmed cell death (PCD) of RECs and address this paradox. Methods: Human RECs and Müller cells were incubated with CD154 and L-N6-(1-Iminoethyl)lysine (L-Nil, nitric oxide synthase 2 inhibitor), α-lipoic acid (inhibitor of oxidative stress), anti-Fas ligand antibody, or A-438079 (P2X7 adenosine triphosphate [ATP] receptor inhibitor)...
November 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27892542/streptococcus-pneumoniae-disrupts-pulmonary-immune-defence-via-elastase-release-following-pneumolysin-dependent-neutrophil-lysis
#4
Hisanori Domon, Masataka Oda, Tomoki Maekawa, Kosuke Nagai, Wataru Takeda, Yutaka Terao
Streptococcus pneumoniae is a leading cause of bacterial pneumonia and is the principal cause of morbidity and mortality worldwide. Previous studies suggested that excessive activation of neutrophils results in the release of neutrophil elastase, which contributes to lung injury in severe pneumonia. Although both pneumococcal virulence factors and neutrophil elastase contribute to the development and progression of pneumonia, there are no studies analysing relationships between these factors. Here, we showed that pneumolysin, a pneumococcal pore-forming toxin, induced cell lysis in primary isolated human neutrophils, leading to the release of neutrophil elastase...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27884379/purinergic-signalling-in-autoimmunity-a-role-for-the-p2x7r-in-systemic-lupus-erythematosus
#5
REVIEW
Francesco Di Virgilio, Anna Lisa Giuliani
Purinergic signalling plays a crucial role in immunity and autoimmunity. Among purinergic receptors, the P2X7 receptor (P2X7R) has an undisputed role as it is expressed to high level by immune cells, triggers cytokine release and modulates immune cell differentiation. In this review, we focus on evidence supporting a possible role of the P2X7R in the pathogenesis of systemic lupus erythematosus (SLE).
October 2016: Biomedical Journal
https://www.readbyqxmd.com/read/27884378/purinergic-signaling-in-schistosomal-infection
#6
REVIEW
Claudia Lucia Martins Silva
Human schistosomiasis is a chronic inflammatory disease caused by blood fluke worms belonging to the genus Schistosoma. Health metrics indicate that the disease is related to an elevated number of years lost-to-disability and years lost-to-life. Schistosomiasis is an intravascular disease that is related to a Th1 and Th2 immune response polarization, and the degree of polarization affects the outcome of the disease. The purinergic system is composed of adenosine and nucleotides acting as key messenger molecules...
October 2016: Biomedical Journal
https://www.readbyqxmd.com/read/27884376/purinergic-signaling-in-infection-and-autoimmune-disease
#7
EDITORIAL
Luiz Eduardo Baggio Savio, Robson Coutinho-Silva
Purinergic signaling plays a key role in inflammatory processes and modulates immune responses against a variety of bacterial and eukaryotic parasites. Here we highlight the role of purinergic receptor activation in infection and autoimmune diseases. Purinergic signaling and inflammasomes modulate the host immune response against chlamydial infections. In addition, increasing evidence suggests that purinergic signaling contributes to Schistosomiasis morbidity, a neglected tropical disease caused by parasitic worms called schistosomes...
October 2016: Biomedical Journal
https://www.readbyqxmd.com/read/27883084/nucleoside-diphosphate-kinase-of-p-gingivalis-is-secreted-from-epithelial-cells-in-the-absence-of-a-leader-sequence-through-a-pannexin-1-interactome
#8
Kalina Atanasova, Jungnam Lee, JoAnn Roberts, Kyulim Lee, David M Ojcius, Özlem Yilmaz
Nucleoside-diphosphate-kinases (NDKs) are leaderless, multifunctional enzymes. The mode(s) of NDK secretion is currently undefined, while extracellular translocation of bacterial NDKs is critical for avoidance of host pathogen clearance by opportunistic pathogens such as Porphyromonas gingivalis. P. gingivalis-NDK during infection inhibits extracellular-ATP (eATP)/P2X7-receptor mediated cell death in gingival epithelial cells (GECs) via eATP hydrolysis. Furthermore, depletion of pannexin-1-hemichannel (PNX1) coupled with P2X7-receptor blocks the infection-induced eATP release in GECs, and P...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881823/nanobodies-that-block-gating-of-the-p2x7-ion-channel-ameliorate-inflammation
#9
Welbeck Danquah, Catherine Meyer-Schwesinger, Björn Rissiek, Carolina Pinto, Arnau Serracant-Prat, Miriam Amadi, Domenica Iacenda, Jan-Hendrik Knop, Anna Hammel, Philine Bergmann, Nicole Schwarz, Joana Assunção, Wendy Rotthier, Friedrich Haag, Eva Tolosa, Peter Bannas, Eric Boué-Grabot, Tim Magnus, Toon Laeremans, Catelijne Stortelers, Friedrich Koch-Nolte
Ion channels are desirable therapeutic targets, yet ion channel-directed drugs with high selectivity and few side effects are still needed. Unlike small-molecule inhibitors, antibodies are highly selective for target antigens but mostly fail to antagonize ion channel functions. Nanobodies-small, single-domain antibody fragments-may overcome these problems. P2X7 is a ligand-gated ion channel that, upon sensing adenosine 5'-triphosphate released by damaged cells, initiates a proinflammatory signaling cascade, including release of cytokines, such as interleukin-1β (IL-1β)...
November 23, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27866341/the-role-of-the-p2x7-receptor-in-murine-cutaneous-leishmaniasis-aspects-of-inflammation-and-parasite-control
#10
Vanessa Ribeiro Figliuolo, Suzana Passos Chaves, Luiz Eduardo Baggio Savio, Maria Luiza Prates Thorstenberg, Érika Machado Salles, Christina Maeda Takiya, Maria Regina D'Império-Lima, Herbert Leonel de Matos Guedes, Bartira Rossi-Bergmann, Robson Coutinho-Silva
Leishmania amazonensis is the etiological agent of diffuse cutaneous leishmaniasis. The immunopathology of leishmaniasis caused by L. amazonensis infection is dependent on the pathogenic role of effector CD4(+) T cells. Purinergic signalling has been implicated in resistance to infection by different intracellular parasites. In this study, we evaluated the role of the P2X7 receptor in modulating the immune response and susceptibility to infection by L. amazonensis. We found that P2X7-deficient mice are more susceptible to L...
November 19, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27858314/genetically-dissecting-p2rx7-expression-within-the-central-nervous-system-using-conditional-humanized-mice
#11
Michael W Metzger, Sandra M Walser, Fernando Aprile-Garcia, Nina Dedic, Alon Chen, Florian Holsboer, Eduardo Arzt, Wolfgang Wurst, Jan M Deussing
The purinergic P2X7 receptor (P2X7R) has attracted considerable interest as a potential target for various central nervous system (CNS) pathologies including affective and neurodegenerative disorders. To date, the distribution and cellular localization of the P2X7R in the brain are not fully resolved and a matter of debate mainly due to the limitations of existing tools. However, this knowledge should be a prerequisite for understanding the contribution of the P2X7R to brain disease. Here, we generated a genetic mouse model by humanizing the P2X7R in the mouse as mammalian model organism...
November 17, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27856358/p2x7rs-are-involved-in-cell-death-growth-and-cellular-signaling-in-primary-human-osteoblasts
#12
Ankita Agrawal, Zanne Henriksen, Susanne Syberg, Solveig Petersen, Derya Aslan, Marie Solgaard, Nis Nissen, Tommy Korsgaard Larsen, Peter Schwarz, Thomas H Steinberg, Niklas Rye Jørgensen
The ionotropic ATP-gated P2X7 receptor (P2X7R) is involved in the regulation of many physiological functions including bone metabolism. Several studies on osteoblasts from rodents and human osteoblast-like cell lines have addressed the expression and function of P2X7R on these bone-forming cells however; its role in human primary osteoblasts has not yet been reported. The aim of this study was to assess the expression of the P2X7R in bone marrow-derived stromal cells and in primary human trabecular osteoblasts and to determine the function in bone formation and cell signaling...
November 14, 2016: Bone
https://www.readbyqxmd.com/read/27843532/nlrp3-inflammasome-activation-in-the-brain-after-global-cerebral-ischemia-and-regulation-by-17%C3%AE-estradiol
#13
Roshni Thakkar, Ruimin Wang, Gangadhara Sareddy, Jing Wang, Dharma Thiruvaiyaru, Ratna Vadlamudi, Quanguang Zhang, Darrell Brann
17β-Estradiol (E2) is a well-known neuroprotective factor in the brain. Recently, our lab demonstrated that the neuroprotective and cognitive effects of E2 require mediation by the estrogen receptor (ER) coregulator protein and proline-, glutamic acid-, and leucine-rich protein 1 (PELP1). In the current study, we examined whether E2, acting via PELP1, can exert anti-inflammatory effects in the ovariectomized rat and mouse hippocampus to regulate NLRP3 inflammasome activation after global cerebral ischemia (GCI)...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27834382/erratum-activation-of-p2x7-and-p2y11-purinergic-receptors-inhibits-migration-and-normalizes-tumor-derived-endothelial-cells-via-camp-signaling
#14
D Avanzato, T Genova, A Fiorio Pla, M Bernardini, S Bianco, B Bussolati, D Mancardi, E Giraudo, F Maione, P Cassoni, I Castellano, L Munaron
No abstract text is available yet for this article.
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27833023/p2x7-from-j774-murine-macrophages-acts-as-a-scavenger-receptor-for-bacteria-but-not-yeast
#15
Gabriela Pérez-Flores, Cesar Hernández-Silva, Guadalupe Gutiérrez-Escobedo, Alejandro De Las Peñas, Irene Castaño, Jorge Arreola, Patricia Pérez-Cornejo
We studied the effects of extracellular ATP and Ca(2+) on uptake of bacteria (Staphylococcus aureus or Escherichia coli) and live yeast (Candida glabrata) by J774 macrophages to determine the role of endogenous P2X7 receptors in phagocytosis. Our findings show that phagocytosis of bio-particles coated with S. aureus or E. coli was blocked by ATP and the P2X7 receptor agonist BzATP, while yeast phagocytosis was not. A438079, an antagonist of P2X7 receptors, partially reverted the effects of ATP on bacterial phagocytosis...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27826687/erratum-to-lack-of-functional-p2x7-receptor-aggravates-brain-edema-development-after-middle-cerebral-artery-occlusion
#16
Melanie Kaiser, Anja Penk, Heike Franke, Ute Krügel, Wolfgang Nörenberg, Daniel Huster, Michael Schaefer
No abstract text is available yet for this article.
November 8, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27824163/the-role-of-p2x7-receptors-in-a-rodent-pcp-induced-schizophrenia-model
#17
Bence Koványi, Cecilia Csölle, Stefano Calovi, Adrienn Hanuska, Erzsébet Kató, László Köles, Anindya Bhattacharya, József Haller, Beáta Sperlágh
P2X7 receptors (P2X7Rs) are ligand-gated ion channels sensitive to extracellular ATP. Here we examined for the first time the role of P2X7R in an animal model of schizophrenia. Using the PCP induced schizophrenia model we show that both genetic deletion and pharmacological inhibition of P2X7Rs alleviate schizophrenia-like behavioral alterations. In P2rx7+/+ mice, PCP induced hyperlocomotion, stereotype behavior, ataxia and social withdrawal. In P2X7 receptor deficient mice (P2rx7-/-), the social interactions were increased, whereas the PCP induced hyperlocomotion and stereotype behavior were alleviated...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27823931/two-p2x1-receptor-transcripts-able-to-form-functional-channels-are-present-in-most-human-monocytes
#18
Cintya López-López, Josue Jaramillo-Polanco, Diana P Portales-Pérez, Karen S Gómez-Coronado, Jessica G Rodríguez-Meléndez, Juan D Cortés-García, Rosa Espinosa-Luna, Luis M Montaño, Carlos Barajas-López
To characterize the presence and general properties of P2X1 receptors in single human monocytes we used RT-PCR, flow cytometry, and the patch-clamp and the two-electrode voltage-clamp techniques. Most human monocytes expressed the canonical P2X1 (90%) and its splicing variant P2X1del (88%) mRNAs. P2X1 receptor immunoreactivity was also observed in 70% of these cells. Currents mediated by P2X1 (EC50=1.9±0.8µm) and P2X1del (EC50 >1000µm) channels, expressed in Xenopus leavis oocytes, have different ATP sensitivity and kinetics...
December 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27818661/the-role-of-purine-metabolites-as-damps-in-acute-graft-versus-host-disease
#19
REVIEW
Petya Apostolova, Robert Zeiser
Acute graft-versus-host disease (GvHD) causes high mortality in patients undergoing allogeneic hematopoietic cell transplantation. An early event in the classical pathogenesis of acute GvHD is tissue damage caused by the conditioning treatment or infection that consecutively leads to translocation of bacterial products [pathogen-associated molecular patterns (PAMPs)] into blood or lymphoid tissue, as well as danger-associated molecular patterns (DAMPs), mostly intracellular components that act as pro-inflammatory agents, once they are released into the extracellular space...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27818192/intra-articular-blockade-of-p2x7-receptor-reduces-the-articular-hyperalgesia-and-inflammation-in-the-knee-joint-synovitis-especially-in-female-rats
#20
Juliana Maia Teixeira, Elayne Vieira Dias, Carlos Amílcar Parada, Cláudia Herrera Tambeli
: Synovitis is a key factor in joint diseases pathophysiology, which affects a greater proportion of women than men. P2X7 receptor activation contributes to arthritis, but whether it plays a role in articular inflammatory pain in a sex-dependent manner is unknown. We investigated whether the P2X7 receptor blockade in the knee joint of male and female rats reduces the articular hyperalgesia and inflammation induced by carrageenan knee joint synovitis model. Articular hyperalgesia was quantified using the rat knee joint incapacitation test and the knee joint inflammation, characterized by the concentration of cytokines TNF-α, IL-1β, IL-6 and CINC-1 and by neutrophil migration, was quantified by ELISA and by myeloperoxidase enzyme activity measurement, respectively...
November 3, 2016: Journal of Pain: Official Journal of the American Pain Society
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