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Increased susceptibility to bladder inflammation in smokers: targeting the PAF–PAF receptor interaction to manage inflammatory cell recruitment

Chronic bladder inflammation can result in a significant reduction in quality of life. Smoking remains a leading preventable risk factor in many diseases. Despite the large amount of evidence supporting the risks of smoking, roughly 45 million people in the United States remain smokers. The impact o...

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Detalles Bibliográficos
Autores principales: Marentette, John, Kolar, Grant, McHowat, Jane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760457/
https://www.ncbi.nlm.nih.gov/pubmed/26660553
http://dx.doi.org/10.14814/phy2.12641
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author Marentette, John
Kolar, Grant
McHowat, Jane
author_facet Marentette, John
Kolar, Grant
McHowat, Jane
author_sort Marentette, John
collection PubMed
description Chronic bladder inflammation can result in a significant reduction in quality of life. Smoking remains a leading preventable risk factor in many diseases. Despite the large amount of evidence supporting the risks of smoking, roughly 45 million people in the United States remain smokers. The impact of cigarette smoking on inflammation is well established, but how smoking promotes bladder inflammation is currently unknown. The aim of this study was to determine if cigarette smoke exposure impacts inflammatory cell adherence to bladder endothelial cells and if targeting the platelet‐activating factor (PAF)–PAF receptor (PAFR) interaction could be beneficial in managing bladder inflammation. In response to cigarette smoke extract (CSE) incubation, bladder endothelial cells from human or mouse displayed increased PAF accumulation, decreased PAF‐AH activity, and increased inflammatory cell adherence. Inhibition of endothelial cell calcium‐independent phospholipase A(2) β (iPLA (2) β) with (S)‐BEL, to block PAF production, prevented adherence of inflammatory cells. Pretreatment of inflammatory cells with PAFR antagonists, ginkgolide B or WEB2086 significantly reduced the number of adhered cells to bladder endothelium. Wild‐type mice exposed to cigarette smoke displayed increased presence of inflammatory infiltration which was absent in iPLA (2) β (−/−) mice and those exposed to room air. In conclusion, cigarette smoke exposure increases endothelial cell PAF accumulation and increased inflammatory cell adherence. Inhibition of PAF accumulation or PAFR antagonism markedly attenuated inflammatory cell adherence to bladder endothelial cells. The results detailed in this study highlight to potential therapeutic targets for managing bladder inflammation.
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spelling pubmed-47604572016-02-22 Increased susceptibility to bladder inflammation in smokers: targeting the PAF–PAF receptor interaction to manage inflammatory cell recruitment Marentette, John Kolar, Grant McHowat, Jane Physiol Rep Original Research Chronic bladder inflammation can result in a significant reduction in quality of life. Smoking remains a leading preventable risk factor in many diseases. Despite the large amount of evidence supporting the risks of smoking, roughly 45 million people in the United States remain smokers. The impact of cigarette smoking on inflammation is well established, but how smoking promotes bladder inflammation is currently unknown. The aim of this study was to determine if cigarette smoke exposure impacts inflammatory cell adherence to bladder endothelial cells and if targeting the platelet‐activating factor (PAF)–PAF receptor (PAFR) interaction could be beneficial in managing bladder inflammation. In response to cigarette smoke extract (CSE) incubation, bladder endothelial cells from human or mouse displayed increased PAF accumulation, decreased PAF‐AH activity, and increased inflammatory cell adherence. Inhibition of endothelial cell calcium‐independent phospholipase A(2) β (iPLA (2) β) with (S)‐BEL, to block PAF production, prevented adherence of inflammatory cells. Pretreatment of inflammatory cells with PAFR antagonists, ginkgolide B or WEB2086 significantly reduced the number of adhered cells to bladder endothelium. Wild‐type mice exposed to cigarette smoke displayed increased presence of inflammatory infiltration which was absent in iPLA (2) β (−/−) mice and those exposed to room air. In conclusion, cigarette smoke exposure increases endothelial cell PAF accumulation and increased inflammatory cell adherence. Inhibition of PAF accumulation or PAFR antagonism markedly attenuated inflammatory cell adherence to bladder endothelial cells. The results detailed in this study highlight to potential therapeutic targets for managing bladder inflammation. John Wiley and Sons Inc. 2015-12-10 /pmc/articles/PMC4760457/ /pubmed/26660553 http://dx.doi.org/10.14814/phy2.12641 Text en © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Marentette, John
Kolar, Grant
McHowat, Jane
Increased susceptibility to bladder inflammation in smokers: targeting the PAF–PAF receptor interaction to manage inflammatory cell recruitment
title Increased susceptibility to bladder inflammation in smokers: targeting the PAF–PAF receptor interaction to manage inflammatory cell recruitment
title_full Increased susceptibility to bladder inflammation in smokers: targeting the PAF–PAF receptor interaction to manage inflammatory cell recruitment
title_fullStr Increased susceptibility to bladder inflammation in smokers: targeting the PAF–PAF receptor interaction to manage inflammatory cell recruitment
title_full_unstemmed Increased susceptibility to bladder inflammation in smokers: targeting the PAF–PAF receptor interaction to manage inflammatory cell recruitment
title_short Increased susceptibility to bladder inflammation in smokers: targeting the PAF–PAF receptor interaction to manage inflammatory cell recruitment
title_sort increased susceptibility to bladder inflammation in smokers: targeting the paf–paf receptor interaction to manage inflammatory cell recruitment
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760457/
https://www.ncbi.nlm.nih.gov/pubmed/26660553
http://dx.doi.org/10.14814/phy2.12641
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