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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Journal ArticleDOI
Type 1 TNF receptor forms a complex with and uses Jak2 and c-Src to selectively engage signaling pathways that regulate transcription factor activity.
TL;DR: The observations show that TNFR1 associates with and uses nonreceptor tyrosine kinases to engage signaling pathways, activate transcription factors, and modulate gene expression in cells.
Journal ArticleDOI
Pannexin 1 channels link chemoattractant receptor signaling to local excitation and global inhibition responses at the front and back of polarized neutrophils.
TL;DR: The findings suggest that chemoattractant receptors require PANX1 to trigger excitatory and inhibitory signals that synergize to fine-tune chemotactic responses at the front and back of neutrophils.
Journal ArticleDOI
Purinergic P2Y2 Receptors Promote Neutrophil Infiltration and Hepatocyte Death in Mice With Acute Liver Injury
Cemil Korcan Ayata,Stephanie C. Ganal,Birgit Hockenjos,Karolina Willim,Rodolfo de Paula Vieira,Melanie Grimm,Bernard Robaye,Jean-Marie Boeynaems,Francesco Di Virgilio,Patrizia Pellegatti,Andreas Diefenbach,Marco Idzko,Peter Hasselblatt +12 more
TL;DR: Analysis of liver-infiltrating immune cells during acute hepatitis revealed that expression of P2Y(2)R in bone marrow-derived cells was required for liver infiltration by neutrophils and subsequent liver damage.
Journal ArticleDOI
The role of pannexin1 in the induction and resolution of inflammation
TL;DR: Together, Panx1, ATP, purinergic receptors, and ectonucleotidases contribute to important feedback loops during the inflammatory response, and thus represent promising candidates for new therapies.
Journal ArticleDOI
Major Contribution of the P2Y1 Receptor in Purinergic Regulation of TNFα-Induced Vascular Inflammation
Murielle Zerr,Béatrice Hechler,Monique Freund,Stéphanie Magnenat,Isabelle Lanois,J.-P. Cazenave,Catherine Léon,Christian Gachet +7 more
TL;DR: It is shown that the P2Y1 receptor plays a role in leukocyte recruitment in inflamed mouse femoral arteries of apolipoprotein E–deficient mice, highlighting a key role of the endothelial P2y1 receptor in acute vascular inflammation.
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