Cargando…

Aspirin Intolerance: Experimental Models for Bed-to-Bench

Aspirin is the oldest non-steroidal anti-inflammatory drug (NSAID), and it sometimes causes asthma-like symptoms known as aspirin-exacerbated respiratory disease (AERD), which can be serious. Unwanted effects of aspirin (aspirin intolerance) are also observed in patients with food-dependent exercise...

Descripción completa

Detalles Bibliográficos
Autor principal: Yamashita, Masamichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Science Publishers 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345322/
https://www.ncbi.nlm.nih.gov/pubmed/27719658
http://dx.doi.org/10.2174/1389450117666161005152327
_version_ 1782513695286362112
author Yamashita, Masamichi
author_facet Yamashita, Masamichi
author_sort Yamashita, Masamichi
collection PubMed
description Aspirin is the oldest non-steroidal anti-inflammatory drug (NSAID), and it sometimes causes asthma-like symptoms known as aspirin-exacerbated respiratory disease (AERD), which can be serious. Unwanted effects of aspirin (aspirin intolerance) are also observed in patients with food-dependent exercise-induced anaphylaxis, a type I allergy disease, and aspirin-induced urticaria (AIU). However the target and the mechanism of the aspirin intolerance are still unknown. There is no animal or cellular model of AERD, because its pathophysiological mechanism is still unknown, but it is thought that inhibition of cyclooxygenase by causative agents leads to an increase of free arachidonic acid, which is metabolized into cysteinyl leukotrienes (cysLTs) that provoke airway smooth muscle constriction and asthma symptoms. As the bed-to-bench approach, to confirm the clinical discussion in experimental cellular models, we have tried to develop a cellular model of AERD using activated RBL-2H3 cells, a rat mast cell like cell line. Indomethacin (another NSAID and also causes AERD), enhances in vitro cysLTs production by RBL-2H3 cells, while there is no induction of cysLTs production in the absence of inflammatory activation. Since this suggests that all inflammatory cells with activation of prostaglandin and cysLT metabolism should respond to NSAIDs, and then I have concluded that aspirin intolerance should be separated from subsequent bronchoconstriction. Evidence about the cellular mechanisms of NSAIDs may be employed for development of in vitro AERD models as the approach from bench-to-bed.
format Online
Article
Text
id pubmed-5345322
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Bentham Science Publishers
record_format MEDLINE/PubMed
spelling pubmed-53453222017-03-29 Aspirin Intolerance: Experimental Models for Bed-to-Bench Yamashita, Masamichi Curr Drug Targets Article Aspirin is the oldest non-steroidal anti-inflammatory drug (NSAID), and it sometimes causes asthma-like symptoms known as aspirin-exacerbated respiratory disease (AERD), which can be serious. Unwanted effects of aspirin (aspirin intolerance) are also observed in patients with food-dependent exercise-induced anaphylaxis, a type I allergy disease, and aspirin-induced urticaria (AIU). However the target and the mechanism of the aspirin intolerance are still unknown. There is no animal or cellular model of AERD, because its pathophysiological mechanism is still unknown, but it is thought that inhibition of cyclooxygenase by causative agents leads to an increase of free arachidonic acid, which is metabolized into cysteinyl leukotrienes (cysLTs) that provoke airway smooth muscle constriction and asthma symptoms. As the bed-to-bench approach, to confirm the clinical discussion in experimental cellular models, we have tried to develop a cellular model of AERD using activated RBL-2H3 cells, a rat mast cell like cell line. Indomethacin (another NSAID and also causes AERD), enhances in vitro cysLTs production by RBL-2H3 cells, while there is no induction of cysLTs production in the absence of inflammatory activation. Since this suggests that all inflammatory cells with activation of prostaglandin and cysLT metabolism should respond to NSAIDs, and then I have concluded that aspirin intolerance should be separated from subsequent bronchoconstriction. Evidence about the cellular mechanisms of NSAIDs may be employed for development of in vitro AERD models as the approach from bench-to-bed. Bentham Science Publishers 2016-12 2016-12 /pmc/articles/PMC5345322/ /pubmed/27719658 http://dx.doi.org/10.2174/1389450117666161005152327 Text en © 2016 Bentham Science Publishers https://creativecommons.org/licenses/by-nc/4.0/legalcode This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
spellingShingle Article
Yamashita, Masamichi
Aspirin Intolerance: Experimental Models for Bed-to-Bench
title Aspirin Intolerance: Experimental Models for Bed-to-Bench
title_full Aspirin Intolerance: Experimental Models for Bed-to-Bench
title_fullStr Aspirin Intolerance: Experimental Models for Bed-to-Bench
title_full_unstemmed Aspirin Intolerance: Experimental Models for Bed-to-Bench
title_short Aspirin Intolerance: Experimental Models for Bed-to-Bench
title_sort aspirin intolerance: experimental models for bed-to-bench
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345322/
https://www.ncbi.nlm.nih.gov/pubmed/27719658
http://dx.doi.org/10.2174/1389450117666161005152327
work_keys_str_mv AT yamashitamasamichi aspirinintoleranceexperimentalmodelsforbedtobench