TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins
| Autor: | Alicia Sanchez, Otto Fajardo, José R. López-López, Rosa Señarís, Bristol Denlinger, Sendoa Tajada, Carlos Belmonte, Karel Talavera, Tatiana Kichko, Víctor M. Meseguer, Enoch Luis, Yeranddy A. Alpizar, Arturo Talavera, Belén Navia, Peter W. Reeh, Félix Viana, Thomas Voets, Carlos Fernández-Peña, Jan-Albert Manenschijn, M. T. Pérez-García |
|---|---|
| Přispěvatelé: | Generalitat Valenciana, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Fundación Botín, Gouvernement fédéral belge, Research Foundation - Flanders, University of Leuven |
| Rok vydání: | 2013 |
| Předmět: |
Lipopolysaccharides
Sensory Receptor Cells General Physics and Astronomy Pain Inflammation CHO Cells Biology General Biochemistry Genetics and Molecular Biology Article Membrane Potentials Transient receptor potential channel Cricetulus Transient Receptor Potential Channels Infección bacteriana Cricetinae medicine Escherichia coli Animals Humans TRPA1 Cation Channel Sensitization Mice Knockout Neurogenic inflammation Multidisciplinary Cell Membrane Neuropeptides Nociceptors Visceral pain General Chemistry Patogénesis Mice Inbred C57BL Toll-Like Receptor 4 Nociception medicine.anatomical_structure HEK293 Cells Lipid A nervous system Immunology TLR4 Nociceptor medicine.symptom Neurogenic Inflammation Ion Channel Gating Signal Transduction |
| Zdroj: | Nature Communications Digital.CSIC. Repositorio Institucional del CSIC instname UVaDOC. Repositorio Documental de la Universidad de Valladolid |
| ISSN: | 2041-1723 |
| Popis: | This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.-- et al. Gram-negative bacterial infections are accompanied by inflammation and somatic or visceral pain. These symptoms are generally attributed to sensitization of nociceptors by inflammatory mediators released by immune cells. Nociceptor sensitization during inflammation occurs through activation of the Toll-like receptor 4 (TLR4) signalling pathway by lipopolysaccharide (LPS), a toxic by-product of bacterial lysis. Here we show that LPS exerts fast, membrane delimited, excitatory actions via TRPA1, a transient receptor potential cation channel that is critical for transducing environmental irritant stimuli into nociceptor activity. Moreover, we find that pain and acute vascular reactions, including neurogenic inflammation (CGRP release) caused by LPS are primarily dependent on TRPA1 channel activation in nociceptive sensory neurons, and develop independently of TLR4 activation. The identification of TRPA1 as a molecular determinant of direct LPS effects on nociceptors offers new insights into the pathogenesis of pain and neurovascular responses during bacterial infections and opens novel avenues for their treatment. © 2014 Macmillan Publishers Limited. All rights reserved. O.F. and C.F.P. were predoctoral students of the Generalitat Valenciana. S.T., B.D., V.M. and J.A.M. were supported by predoctoral fellowships from the Spanish MINECO. Research was supported by Spanish public funds projects SAF2010-14990 and PROMETEO2010-046 to F.V., BFU2007-61524 to J.R.L.L., BFU2010-15898 to M.T.P.G., Instituto de Salud Carlos III PI12/00586 to R.S., BFU2005-08741 and CONSOLIDER-INGENIO 2010 CSD2007-00023 to C.B., ISCIII grants R006/009 (Red Heracles), the Spanish Fundación Marcelino Botín and Belgian Federal Government (IUAP P6/28 and P7/13), the Research Foundation-Flanders (F.W.O. G.0565.07, G.0686.09, G.A022.11N and G.0702.12), and the Research Council of the KU Leuven (GOA 2009/07, EF/95/010, PFV/10/006, OT/12/091 and GOA 14011). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|