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Expression and activation of the oxytocin receptor in airway smooth muscle cells: Regulation by TNFα and IL-13

BACKGROUND: During pregnancy asthma may remain stable, improve or worsen. The factors underlying the deleterious effect of pregnancy on asthma remain unknown. Oxytocin is a neurohypophyseal protein that regulates a number of central and peripheral responses such as uterine contractions and milk ejec...

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Autores principales: Amrani, Yassine, Syed, Farhat, Huang, Chris, Li, Katherine, Liu, Veronica, Jain, Deepika, Keslacy, Stefan, Sims, Michael W, Baidouri, Hasna, Cooper, Philip R, Zhao, Hengjiang, Siddiqui, Salman, Brightling, Christopher E, Griswold, Don, Li, Lily, Panettieri, Reynold A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922094/
https://www.ncbi.nlm.nih.gov/pubmed/20670427
http://dx.doi.org/10.1186/1465-9921-11-104
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author Amrani, Yassine
Syed, Farhat
Huang, Chris
Li, Katherine
Liu, Veronica
Jain, Deepika
Keslacy, Stefan
Sims, Michael W
Baidouri, Hasna
Cooper, Philip R
Zhao, Hengjiang
Siddiqui, Salman
Brightling, Christopher E
Griswold, Don
Li, Lily
Panettieri, Reynold A
author_facet Amrani, Yassine
Syed, Farhat
Huang, Chris
Li, Katherine
Liu, Veronica
Jain, Deepika
Keslacy, Stefan
Sims, Michael W
Baidouri, Hasna
Cooper, Philip R
Zhao, Hengjiang
Siddiqui, Salman
Brightling, Christopher E
Griswold, Don
Li, Lily
Panettieri, Reynold A
author_sort Amrani, Yassine
collection PubMed
description BACKGROUND: During pregnancy asthma may remain stable, improve or worsen. The factors underlying the deleterious effect of pregnancy on asthma remain unknown. Oxytocin is a neurohypophyseal protein that regulates a number of central and peripheral responses such as uterine contractions and milk ejection. Additional evidence suggests that oxytocin regulates inflammatory processes in other tissues given the ubiquitous expression of the oxytocin receptor. The purpose of this study was to define the role of oxytocin in modulating human airway smooth muscle (HASMCs) function in the presence and absence of IL-13 and TNFα, cytokines known to be important in asthma. METHOD: Expression of oxytocin receptor in cultured HASMCs was performed by real time PCR and flow cytomery assays. Responses to oxytocin was assessed by fluorimetry to detect calcium signals while isolated tracheal rings and precision cut lung slices (PCLS) were used to measure contractile responses. Finally, ELISA was used to compare oxytocin levels in the bronchoalveloar lavage (BAL) samples from healthy subjects and those with asthma. RESULTS: PCR analysis demonstrates that OXTR is expressed in HASMCs under basal conditions and that both interleukin (IL)-13 and tumor necrosis factor (TNFα) stimulate a time-dependent increase in OXTR expression at 6 and 18 hr. Additionally, oxytocin increases cytosolic calcium levels in fura-2-loaded HASMCs that were enhanced in cells treated for 24 hr with IL-13. Interestingly, TNFα had little effect on oxytocin-induced calcium response despite increasing receptor expression. Using isolated murine tracheal rings and PCLS, oxytocin also promoted force generation and airway narrowing. Further, oxytocin levels are detectable in bronchoalveolar lavage (BAL) fluid derived from healthy subjects as well as from those with asthma. CONCLUSION: Taken together, we show that cytokines modulate the expression of functional oxytocin receptors in HASMCs suggesting a potential role for inflammation-induced changes in oxytocin receptor signaling in the regulation of airway hyper-responsiveness in asthma.
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spelling pubmed-29220942010-08-17 Expression and activation of the oxytocin receptor in airway smooth muscle cells: Regulation by TNFα and IL-13 Amrani, Yassine Syed, Farhat Huang, Chris Li, Katherine Liu, Veronica Jain, Deepika Keslacy, Stefan Sims, Michael W Baidouri, Hasna Cooper, Philip R Zhao, Hengjiang Siddiqui, Salman Brightling, Christopher E Griswold, Don Li, Lily Panettieri, Reynold A Respir Res Research BACKGROUND: During pregnancy asthma may remain stable, improve or worsen. The factors underlying the deleterious effect of pregnancy on asthma remain unknown. Oxytocin is a neurohypophyseal protein that regulates a number of central and peripheral responses such as uterine contractions and milk ejection. Additional evidence suggests that oxytocin regulates inflammatory processes in other tissues given the ubiquitous expression of the oxytocin receptor. The purpose of this study was to define the role of oxytocin in modulating human airway smooth muscle (HASMCs) function in the presence and absence of IL-13 and TNFα, cytokines known to be important in asthma. METHOD: Expression of oxytocin receptor in cultured HASMCs was performed by real time PCR and flow cytomery assays. Responses to oxytocin was assessed by fluorimetry to detect calcium signals while isolated tracheal rings and precision cut lung slices (PCLS) were used to measure contractile responses. Finally, ELISA was used to compare oxytocin levels in the bronchoalveloar lavage (BAL) samples from healthy subjects and those with asthma. RESULTS: PCR analysis demonstrates that OXTR is expressed in HASMCs under basal conditions and that both interleukin (IL)-13 and tumor necrosis factor (TNFα) stimulate a time-dependent increase in OXTR expression at 6 and 18 hr. Additionally, oxytocin increases cytosolic calcium levels in fura-2-loaded HASMCs that were enhanced in cells treated for 24 hr with IL-13. Interestingly, TNFα had little effect on oxytocin-induced calcium response despite increasing receptor expression. Using isolated murine tracheal rings and PCLS, oxytocin also promoted force generation and airway narrowing. Further, oxytocin levels are detectable in bronchoalveolar lavage (BAL) fluid derived from healthy subjects as well as from those with asthma. CONCLUSION: Taken together, we show that cytokines modulate the expression of functional oxytocin receptors in HASMCs suggesting a potential role for inflammation-induced changes in oxytocin receptor signaling in the regulation of airway hyper-responsiveness in asthma. BioMed Central 2010 2010-07-29 /pmc/articles/PMC2922094/ /pubmed/20670427 http://dx.doi.org/10.1186/1465-9921-11-104 Text en Copyright ©2010 Amrani et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Amrani, Yassine
Syed, Farhat
Huang, Chris
Li, Katherine
Liu, Veronica
Jain, Deepika
Keslacy, Stefan
Sims, Michael W
Baidouri, Hasna
Cooper, Philip R
Zhao, Hengjiang
Siddiqui, Salman
Brightling, Christopher E
Griswold, Don
Li, Lily
Panettieri, Reynold A
Expression and activation of the oxytocin receptor in airway smooth muscle cells: Regulation by TNFα and IL-13
title Expression and activation of the oxytocin receptor in airway smooth muscle cells: Regulation by TNFα and IL-13
title_full Expression and activation of the oxytocin receptor in airway smooth muscle cells: Regulation by TNFα and IL-13
title_fullStr Expression and activation of the oxytocin receptor in airway smooth muscle cells: Regulation by TNFα and IL-13
title_full_unstemmed Expression and activation of the oxytocin receptor in airway smooth muscle cells: Regulation by TNFα and IL-13
title_short Expression and activation of the oxytocin receptor in airway smooth muscle cells: Regulation by TNFα and IL-13
title_sort expression and activation of the oxytocin receptor in airway smooth muscle cells: regulation by tnfα and il-13
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922094/
https://www.ncbi.nlm.nih.gov/pubmed/20670427
http://dx.doi.org/10.1186/1465-9921-11-104
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