Pannexin 1 channels regulate leukocyte emigration through the venous endothelium during acute inflammation.
Alexander W. Lohman,Igor L. Leskov,Joshua T. Butcher,Scott R. Johnstone,Tara A. Stokes,Daniela Begandt,Leon J. DeLalio,Angela K. Best,Silvia Penuela,Norbert Leitinger,Kodi S. Ravichandran,Karen Y. Stokes,Brant E. Isakson +12 more
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TLDR
It is reported that the ATP-release channel Pannexin1 (Panx1) opens downstream of EC activation by TNF-α, placing Panx1 channels at the centre of cytokine crosstalk with purinergic signalling in the endothelium.Abstract:
Inflammatory cell recruitment to local sites of tissue injury and/or infection is controlled by a plethora of signalling processes influencing cell-to-cell interactions between the vascular endothelial cells (ECs) in post-capillary venules and circulating leukocytes. Recently, ATP-sensitive P2Y purinergic receptors have emerged as downstream regulators of EC activation in vascular inflammation. However, the mechanism(s) regulating cellular ATP release in this response remains elusive. Here we report that the ATP-release channel Pannexin1 (Panx1) opens downstream of EC activation by TNF-α. This process involves activation of type-1 TNF receptors, recruitment of Src family kinases (SFK) and SFK-dependent phosphorylation of Panx1. Using an inducible, EC-specific Panx1 knockout mouse line, we report a previously unidentified role for Panx1 channels in promoting leukocyte adhesion and emigration through the venous wall during acute systemic inflammation, placing Panx1 channels at the centre of cytokine crosstalk with purinergic signalling in the endothelium.read more
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Purinergic Signaling in the Cardiovascular System.
TL;DR: The involvement of purinergic signaling in cardiovascular pathophysiology and its therapeutic potential are discussed, including heart failure, infarction, arrhythmias, syncope, cardiomyopathy, angina, heart transplantation and coronary bypass grafts, coronary artery disease, diabetic cardiopathy, hypertension, ischemia, thrombosis, diabetes mellitus, and migraine.
Journal ArticleDOI
TBK1 at the Crossroads of Inflammation and Energy Homeostasis in Adipose Tissue.
Peng Zhao,Kai in Wong,Xiaoli Sun,Shannon M. Reilly,Shannon M. Reilly,Maeran Uhm,Zhongji Liao,Yuliya Skorobogatko,Yuliya Skorobogatko,Alan R. Saltiel,Alan R. Saltiel +10 more
TL;DR: It is reported that the kinase uniquely controls energy metabolism, and a unique role for TBK1 in mediating bidirectional crosstalk between energy sensing and inflammatory signaling pathways in both over- and undernutrition.
Journal ArticleDOI
Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications
Luc Leybaert,Paul D. Lampe,Stefan Dhein,Brenda R. Kwak,Péter Ferdinandy,Eric C. Beyer,Dale W. Laird,Christian C. Naus,Colin R. Green,Rainer Schulz +9 more
TL;DR: It is concluded that peptide-based investigations have raised several new opportunities for interfering with connexins and their channels that may soon allow preservation of gap junction communication, inhibition of hemichannel opening, and mitigation of inflammatory signaling.
Journal ArticleDOI
Mechanisms of ATP Release by Inflammatory Cells
TL;DR: Key effector functions of inflammatory cells are regulated by purinergic signaling in acute and chronic diseases, making extracellular nucleotide release a promising target for the development of new therapies.
Journal ArticleDOI
ATP Release Channels.
TL;DR: Five groups of channels are acknowledged as ATP-release channels: connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1), volume-regulated anion channels (VRACs, also known as volume-sensitive outwardly rectifying (VSOR) anion channel), and maxi-anion channels(MACs), and a discussion on the future implications of understanding these channels are summarized.
References
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Targeted Disruption of cd73/Ecto-5′-Nucleotidase Alters Thromboregulation and Augments Vascular Inflammatory Response
Patrycja Koszalka,Burcin Özüyaman,Yuqing Huo,Alma Zernecke,Ulrich Flögel,Norbert Braun,Anja Buchheiser,Ulrich K. M. Decking,Michael L. Smith,Jean Sévigny,Adrian R.L. Gear,Artur Aron Weber,Andrei Molojavyi,Zhaoping Ding,Christian Weber,Klaus Ley,Herbert Zimmermann,Axel Gödecke,Jürgen Schrader +18 more
TL;DR: The data provide the first evidence that adenosine, extracellularly formed by CD73, can modulate coronary vascular tone, inhibit platelet activation, and play an important role in leukocyte adhesion to the vascular endothelium in vivo.
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A permeant regulating its permeation pore: inhibition of pannexin 1 channels by ATP
Feng Qiu,Gerhard Dahl +1 more
TL;DR: A negative feedback loop controlling pannexin 1 channel activity is described and Mutational analysis identified R75 in pannexIn 1 to be critical for ATP inhibition of pan Nexin 1 currents.
Journal ArticleDOI
Acute Tumor Necrosis Factor Alpha Signaling via NADPH Oxidase in Microvascular Endothelial Cells: Role of p47phox Phosphorylation and Binding to TRAF4
TL;DR: The increased binding between p47phox and TRAF4 that occurs after p 47phox phosphorylation could serve to spatially confine ROS generation from NADPH oxidase and subsequent MAPK activation and cell surface ICAM-1 expression in EC.
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Unexpected link between an antibiotic, pannexin channels and apoptosis
Ivan K. H. Poon,Yu-Hsin Chiu,Allison Armstrong,Jason M. Kinchen,Ignacio J. Juncadella,Douglas A. Bayliss,Kodi S. Ravichandran +6 more
TL;DR: Genetic loss of PANX1 phenocopied trovafloxacin effects is identified, revealing a non-redundant role for pannexin channels in regulating cellular disassembly during apoptosis, and suggesting that re-engineering certain quinolones might help develop newer antibacterials.
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Adenosine and inflammation: CD39 and CD73 are critical mediators in LPS-induced PMN trafficking into the lungs
Jörg Reutershan,Irene Vollmer,Stefanie Stark,Rosalyn Wagner,Kristian-Christos Ngamsri,Holger K. Eltzschig +5 more
TL;DR: Data reveal a previously unrecognized role for CD39 and CD73 in attenuating PMN trafficking into the lungs during LPS‐induced lung injury and suggest treatment with their soluble compounds as a therapeutic strategy.
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