Protease activated receptor-2 expression and function in asthmatic bronchial smooth muscle.

Asthmatic bronchial smooth muscle (BSM) is characterized by structural remodeling associated with mast cell infiltration displaying features of chronic degranulation. Mast cell-derived tryptase can activate protease activated receptor type-2 (PAR-2) of BSM cells. The aims of the present study were (...

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Autores principales:	Benoit Allard, Imane Bara, Guillaume Gilbert, Gabrielle Carvalho, Thomas Trian, Annaig Ozier, Jennifer Gillibert-Duplantier, Olga Ousova, Elise Maurat, Matthieu Thumerel, Jean-François Quignard, Pierre-Olivier Girodet, Roger Marthan, Patrick Berger
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/32d3d3639d524853848b27283d297663
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spelling	oai:doaj.org-article:32d3d3639d524853848b27283d2976632021-11-18T08:32:41ZProtease activated receptor-2 expression and function in asthmatic bronchial smooth muscle.1932-620310.1371/journal.pone.0086945https://doaj.org/article/32d3d3639d524853848b27283d2976632014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24551046/?tool=EBIhttps://doaj.org/toc/1932-6203Asthmatic bronchial smooth muscle (BSM) is characterized by structural remodeling associated with mast cell infiltration displaying features of chronic degranulation. Mast cell-derived tryptase can activate protease activated receptor type-2 (PAR-2) of BSM cells. The aims of the present study were (i) to evaluate the expression of PAR-2 in both asthmatic and non asthmatic BSM cells and, (ii) to analyze the effect of prolonged stimulation of PAR-2 in asthmatic BSM cells on cell signaling and proliferation. BSM cells were obtained from both 33 control subjects and 22 asthmatic patients. PAR-2 expression was assessed by flow cytometry, western blot and quantitative RT-PCR. Calcium response, transduction pathways and proliferation were evaluated before and following PAR-2 stimulation by SLIGKV-NH2 or trypsin for 1 to 3 days. Asthmatic BSM cells expressed higher basal levels of functional PAR-2 compared to controls in terms of mRNA, protein expression and calcium response. When PAR-2 expression was increased by means of lentivirus in control BSM cells to a level similar to that of asthmatic cells, PAR-2-induced calcium response was then similar in both types of cell. However, repeated PAR-2 stimulations increased the proliferation of asthmatic BSM cells but not that of control BSM cells even following lentiviral over-expression of PAR-2. Such an increased proliferation was related to an increased phosphorylation of ERK in asthmatic BSM cells. In conclusion, we have demonstrated that asthmatic BSM cells express increased baseline levels of functional PAR-2. This higher basal level of PAR-2 accounts for the increased calcium response to PAR-2 stimulation, whereas the increased proliferation to repeated PAR-2 stimulation is related to increased ERK phosphorylation.Benoit AllardImane BaraGuillaume GilbertGabrielle CarvalhoThomas TrianAnnaig OzierJennifer Gillibert-DuplantierOlga OusovaElise MauratMatthieu ThumerelJean-François QuignardPierre-Olivier GirodetRoger MarthanPatrick BergerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e86945 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Benoit Allard Imane Bara Guillaume Gilbert Gabrielle Carvalho Thomas Trian Annaig Ozier Jennifer Gillibert-Duplantier Olga Ousova Elise Maurat Matthieu Thumerel Jean-François Quignard Pierre-Olivier Girodet Roger Marthan Patrick Berger Protease activated receptor-2 expression and function in asthmatic bronchial smooth muscle.
description	Asthmatic bronchial smooth muscle (BSM) is characterized by structural remodeling associated with mast cell infiltration displaying features of chronic degranulation. Mast cell-derived tryptase can activate protease activated receptor type-2 (PAR-2) of BSM cells. The aims of the present study were (i) to evaluate the expression of PAR-2 in both asthmatic and non asthmatic BSM cells and, (ii) to analyze the effect of prolonged stimulation of PAR-2 in asthmatic BSM cells on cell signaling and proliferation. BSM cells were obtained from both 33 control subjects and 22 asthmatic patients. PAR-2 expression was assessed by flow cytometry, western blot and quantitative RT-PCR. Calcium response, transduction pathways and proliferation were evaluated before and following PAR-2 stimulation by SLIGKV-NH2 or trypsin for 1 to 3 days. Asthmatic BSM cells expressed higher basal levels of functional PAR-2 compared to controls in terms of mRNA, protein expression and calcium response. When PAR-2 expression was increased by means of lentivirus in control BSM cells to a level similar to that of asthmatic cells, PAR-2-induced calcium response was then similar in both types of cell. However, repeated PAR-2 stimulations increased the proliferation of asthmatic BSM cells but not that of control BSM cells even following lentiviral over-expression of PAR-2. Such an increased proliferation was related to an increased phosphorylation of ERK in asthmatic BSM cells. In conclusion, we have demonstrated that asthmatic BSM cells express increased baseline levels of functional PAR-2. This higher basal level of PAR-2 accounts for the increased calcium response to PAR-2 stimulation, whereas the increased proliferation to repeated PAR-2 stimulation is related to increased ERK phosphorylation.
format	article
author	Benoit Allard Imane Bara Guillaume Gilbert Gabrielle Carvalho Thomas Trian Annaig Ozier Jennifer Gillibert-Duplantier Olga Ousova Elise Maurat Matthieu Thumerel Jean-François Quignard Pierre-Olivier Girodet Roger Marthan Patrick Berger
author_facet	Benoit Allard Imane Bara Guillaume Gilbert Gabrielle Carvalho Thomas Trian Annaig Ozier Jennifer Gillibert-Duplantier Olga Ousova Elise Maurat Matthieu Thumerel Jean-François Quignard Pierre-Olivier Girodet Roger Marthan Patrick Berger
author_sort	Benoit Allard
title	Protease activated receptor-2 expression and function in asthmatic bronchial smooth muscle.
title_short	Protease activated receptor-2 expression and function in asthmatic bronchial smooth muscle.
title_full	Protease activated receptor-2 expression and function in asthmatic bronchial smooth muscle.
title_fullStr	Protease activated receptor-2 expression and function in asthmatic bronchial smooth muscle.
title_full_unstemmed	Protease activated receptor-2 expression and function in asthmatic bronchial smooth muscle.
title_sort	protease activated receptor-2 expression and function in asthmatic bronchial smooth muscle.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/32d3d3639d524853848b27283d297663
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Protease activated receptor-2 expression and function in asthmatic bronchial smooth muscle.

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