Using the one-lung method to link p38 to pro-inflammatory gene expression during overventilation in C57BL/6 and BALB/c mice.

<h4>Introduction</h4>The mechanisms of ventilator-induced lung injury (VILI), including the role of MAP kinases, are frequently studied in different mouse strains. A useful model for such studies is the isolated perfused mouse lung. As a further development we present the one-lung method...

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Autores principales:	Stephanie Siegl, Stefan Uhlig
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8d588001938341c3b9d6d092f61e6a30
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spelling	oai:doaj.org-article:8d588001938341c3b9d6d092f61e6a302021-11-18T07:11:21ZUsing the one-lung method to link p38 to pro-inflammatory gene expression during overventilation in C57BL/6 and BALB/c mice.1932-620310.1371/journal.pone.0041464https://doaj.org/article/8d588001938341c3b9d6d092f61e6a302012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22848503/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Introduction</h4>The mechanisms of ventilator-induced lung injury (VILI), including the role of MAP kinases, are frequently studied in different mouse strains. A useful model for such studies is the isolated perfused mouse lung. As a further development we present the one-lung method that permits to continue perfusion and ventilation of the right lung after removal of the left lung. This method was used to compare the effect of high pressure ventilation (HPV) on pro-inflammatory signaling events in two widely used mouse strains (C57BL/6, BALB/c) and to further define the role of p38 in VILI.<h4>Methods</h4>Lungs were perfused and ventilated for 30 min under control conditions before they were randomized to low (8 cm H(2)O) or high (25 cm H(2)O) pressure ventilation (HPV) for 210 min, with the left lung being removed after 180 min. In the left lung we measured the phosphorylation of p38, JNK, ERK and Akt kinase, and in the right lung gene expression and protein concentrations of Il1b, Il6, Tnf, Cxcl1, Cxcl2, and Areg.<h4>Results</h4>Lung mechanics and kinase activation were similar in both mouse strains. HPV increased all genes (except Tnf in BALB/c) and all mediators in both strains. The gene expression of mRNA for Il1b, Il6, Cxcl1 and Cxcl2 was higher in BALB/c mice. Backward regression of the kinase data at t = 180 min with the gene and protein expression data at t = 240 min suggested that p38 controls HPV-induced gene expression, but not protein production. This hypothesis was confirmed in experiments with the p38-kinase inhibitor SB203580.<h4>Conclusions</h4>The one-lung method is useful for mechanistic studies in the lungs. While C57BL/6 show diminished pro-inflammatory responses during HPV, lung mechanics and mechanotransduction processes appear to be similar in both mouse strains. Finally, the one-lung method allowed us to link p38 to gene expression during VILI.Stephanie SieglStefan UhligPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e41464 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stephanie Siegl Stefan Uhlig Using the one-lung method to link p38 to pro-inflammatory gene expression during overventilation in C57BL/6 and BALB/c mice.
description	<h4>Introduction</h4>The mechanisms of ventilator-induced lung injury (VILI), including the role of MAP kinases, are frequently studied in different mouse strains. A useful model for such studies is the isolated perfused mouse lung. As a further development we present the one-lung method that permits to continue perfusion and ventilation of the right lung after removal of the left lung. This method was used to compare the effect of high pressure ventilation (HPV) on pro-inflammatory signaling events in two widely used mouse strains (C57BL/6, BALB/c) and to further define the role of p38 in VILI.<h4>Methods</h4>Lungs were perfused and ventilated for 30 min under control conditions before they were randomized to low (8 cm H(2)O) or high (25 cm H(2)O) pressure ventilation (HPV) for 210 min, with the left lung being removed after 180 min. In the left lung we measured the phosphorylation of p38, JNK, ERK and Akt kinase, and in the right lung gene expression and protein concentrations of Il1b, Il6, Tnf, Cxcl1, Cxcl2, and Areg.<h4>Results</h4>Lung mechanics and kinase activation were similar in both mouse strains. HPV increased all genes (except Tnf in BALB/c) and all mediators in both strains. The gene expression of mRNA for Il1b, Il6, Cxcl1 and Cxcl2 was higher in BALB/c mice. Backward regression of the kinase data at t = 180 min with the gene and protein expression data at t = 240 min suggested that p38 controls HPV-induced gene expression, but not protein production. This hypothesis was confirmed in experiments with the p38-kinase inhibitor SB203580.<h4>Conclusions</h4>The one-lung method is useful for mechanistic studies in the lungs. While C57BL/6 show diminished pro-inflammatory responses during HPV, lung mechanics and mechanotransduction processes appear to be similar in both mouse strains. Finally, the one-lung method allowed us to link p38 to gene expression during VILI.
format	article
author	Stephanie Siegl Stefan Uhlig
author_facet	Stephanie Siegl Stefan Uhlig
author_sort	Stephanie Siegl
title	Using the one-lung method to link p38 to pro-inflammatory gene expression during overventilation in C57BL/6 and BALB/c mice.
title_short	Using the one-lung method to link p38 to pro-inflammatory gene expression during overventilation in C57BL/6 and BALB/c mice.
title_full	Using the one-lung method to link p38 to pro-inflammatory gene expression during overventilation in C57BL/6 and BALB/c mice.
title_fullStr	Using the one-lung method to link p38 to pro-inflammatory gene expression during overventilation in C57BL/6 and BALB/c mice.
title_full_unstemmed	Using the one-lung method to link p38 to pro-inflammatory gene expression during overventilation in C57BL/6 and BALB/c mice.
title_sort	using the one-lung method to link p38 to pro-inflammatory gene expression during overventilation in c57bl/6 and balb/c mice.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/8d588001938341c3b9d6d092f61e6a30
work_keys_str_mv	AT stephaniesiegl usingtheonelungmethodtolinkp38toproinflammatorygeneexpressionduringoverventilationinc57bl6andbalbcmice AT stefanuhlig usingtheonelungmethodtolinkp38toproinflammatorygeneexpressionduringoverventilationinc57bl6andbalbcmice
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Using the one-lung method to link p38 to pro-inflammatory gene expression during overventilation in C57BL/6 and BALB/c mice.

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