{"id":405,"date":"2013-07-25T17:17:11","date_gmt":"2013-07-25T08:17:11","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=405"},"modified":"2013-07-25T17:17:11","modified_gmt":"2013-07-25T08:17:11","slug":"journal-club-2013-07-26","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=405","title":{"rendered":"Journal club 2013-07-26"},"content":{"rendered":"<div title=\"Page 1\">\n<div>\n<div>\n<p>Human Mas-Related G Protein-Coupled Receptors-X1 Induce Chemokine Receptor 2 Expression in Rat Dorsal Root Ganglia Neurons and Release of Chemokine Ligand 2 from the Human LAD-2 Mast Cell Line<\/p>\n<p><a href=\"http:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2013\/07\/pone.0058756.pdf\">pone.0058756<\/a><\/p>\n<p>Hans Ju \u0308rgen Solinski1, Franziska Petermann2, Kathrin Rothe1, Ingrid Boekhoff1, Thomas Gudermann1, Andreas Breit1*<\/p>\n<p>1Walther-Straub-Institut fu \u0308r Pharmakologie und Toxikologie, Ludwig-Maximilians-Universita \u0308t Mu \u0308nchen, Munich, Germany, 2Department of Neurology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany<\/p>\n<\/div>\n<\/div>\n<table>\n<tbody>\n<tr>\n<td>\n<div>\n<div>\n<p>Abstract<\/p>\n<p>Primate-specific Mas-related G protein-coupled receptors-X1 (MRGPR-X1) are highly enriched in dorsal root ganglia (DRG) neurons and induce acute pain. Herein, we analyzed effects of MRGPR-X1 on serum response factors (SRF) or nuclear factors of activated T cells (NFAT), which control expression of various markers of chronic pain. Using HEK293, DRG neuron-derived F11 cells and cultured rat DRG neurons recombinantly expressing human MRGPR-X1, we found activation of a SRF reporter gene construct and induction of the early growth response protein-1 via extracellular signal-regulated kinases-1\/2 known to play a significant role in the development of inflammatory pain. Furthermore, we observed MRGPR-X1-induced up- regulation of the chemokine receptor 2 (CCR2) via NFAT, which is considered as a key event in the onset of neuropathic pain and, so far, has not yet been described for any endogenous neuropeptide. Up-regulation of CCR2 is often associated with increased release of its endogenous agonist chemokine ligand 2 (CCL2). We also found MRGPR-X1-promoted release of CCL2 in a human connective tissue mast cell line endogenously expressing MRGPR-X1. Thus, we provide first evidence to suggest that MRGPR-X1 induce expression of chronic pain markers in DRG neurons and propose a so far unidentified signaling circuit that enhances chemokine signaling by acting on two distinct yet functionally co-operating cell types. Given the important role of chemokine signaling in pain chronification, we propose that interruption of this signaling circuit might be a promising new strategy to alleviate chemokine-promoted pain.<\/p>\n<\/div>\n<\/div>\n<\/td>\n<\/tr>\n<tr>\n<td>Citation: Solinski HJ, Petermann F, Rothe K, Boekhoff I, Gudermann T, et al. (2013) Human Mas-Related G Protein-Coupled Receptors-X1 Induce Chemokine Receptor 2 Expression in Rat Dorsal Root Ganglia Neurons and Release of Chemokine Ligand 2 from the Human LAD-2 Mast Cell Line. PLoS ONE 8(3): e58756. doi:10.1371\/journal.pone.0058756<\/p>\n<p>Editor: Roland Seifert, Medical School of Hannover, United States of America Received January 18, 2013; Accepted February 6, 2013; Published March 7, 2013<\/p>\n<p>Copyright: \u00df 2013 Solinski et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<\/p>\n<p>Funding: This work was supported by a grant from the \u2018\u2018Deutsche Forschungsgemeinschaft\u2019\u2019 [grant BR 3346\/3\u20131]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.<\/p>\n<p>Competing Interests: The authors have declared that no competing interests exist.*<\/p>\n<p>E-mail: andreas.breit@lrz.uni-muenchen.de<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Human Mas-Related G Protein-Coupled Receptors-X1 Induce Chemokine Receptor 2 Expression in Rat Dorsal Root Ganglia Neurons and Release of Chemokine Ligand 2 from the Human LAD-2 Mast Cell Line pone.0058756 Hans Ju \u0308rgen Solinski1, Franziska Petermann2, Kathrin Rothe1, Ingrid Boekhoff1, Thomas Gudermann1, Andreas Breit1* 1Walther-Straub-Institut fu \u0308r Pharmakologie und Toxikologie, Ludwig-Maximilians-Universita \u0308t Mu \u0308nchen, Munich, [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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