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Differential IL-1 signaling induced by BMPR2 deficiency drives pulmonary vascular remodeling

Bone morphogenetic protein receptor type 2 (BMPR2) mutations are present in patients with heritable and idiopathic pulmonary arterial hypertension (PAH). Circulating levels of interleukin-1 (IL-1) are raised in patients and animal models. Whether interplay between BMP and IL-1 signaling can explain...

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Autores principales: Pickworth, Josephine, Rothman, Alexander, Iremonger, James, Casbolt, Helen, Hopkinson, Kay, Hickey, Peter M., Gladson, Santhi, Shay, Sheila, Morrell, Nicholas W., Francis, Sheila E., West, James D., Lawrie, Allan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703124/
https://www.ncbi.nlm.nih.gov/pubmed/28828907
http://dx.doi.org/10.1177/2045893217729096
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author Pickworth, Josephine
Rothman, Alexander
Iremonger, James
Casbolt, Helen
Hopkinson, Kay
Hickey, Peter M.
Gladson, Santhi
Shay, Sheila
Morrell, Nicholas W.
Francis, Sheila E.
West, James D.
Lawrie, Allan
author_facet Pickworth, Josephine
Rothman, Alexander
Iremonger, James
Casbolt, Helen
Hopkinson, Kay
Hickey, Peter M.
Gladson, Santhi
Shay, Sheila
Morrell, Nicholas W.
Francis, Sheila E.
West, James D.
Lawrie, Allan
author_sort Pickworth, Josephine
collection PubMed
description Bone morphogenetic protein receptor type 2 (BMPR2) mutations are present in patients with heritable and idiopathic pulmonary arterial hypertension (PAH). Circulating levels of interleukin-1 (IL-1) are raised in patients and animal models. Whether interplay between BMP and IL-1 signaling can explain the local manifestation of PAH in the lung remains unclear. Cell culture, siRNA, and mRNA microarray analysis of RNA isolated from human pulmonary artery (PASMC) and aortic (AoSMC) smooth muscle cells were used. R899X(+/–) BMPR2 transgenic mice fed a Western diet for six weeks were given daily injections of IL-1ß prior to assessment for PAH and tissue collection. PASMC have reduced inflammatory activation in response to IL-1ß compared with AoSMCs; however, PASMC with reduced BMPR2 demonstrated an exaggerated response. Mice treated with IL-1ß had higher white blood cell counts and significantly raised serum protein levels of IL-6 and osteoprotegerin (OPG) plasma levels recapitulating in vitro data. Phenotypically, IL-1ß treated mice demonstrated increased pulmonary vascular remodeling. IL-1ß induces an exaggerated pulmonary artery specific transcriptomic inflammatory response when BMPR2 signaling is reduced.
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spelling pubmed-57031242017-12-04 Differential IL-1 signaling induced by BMPR2 deficiency drives pulmonary vascular remodeling Pickworth, Josephine Rothman, Alexander Iremonger, James Casbolt, Helen Hopkinson, Kay Hickey, Peter M. Gladson, Santhi Shay, Sheila Morrell, Nicholas W. Francis, Sheila E. West, James D. Lawrie, Allan Pulm Circ Research Articles Bone morphogenetic protein receptor type 2 (BMPR2) mutations are present in patients with heritable and idiopathic pulmonary arterial hypertension (PAH). Circulating levels of interleukin-1 (IL-1) are raised in patients and animal models. Whether interplay between BMP and IL-1 signaling can explain the local manifestation of PAH in the lung remains unclear. Cell culture, siRNA, and mRNA microarray analysis of RNA isolated from human pulmonary artery (PASMC) and aortic (AoSMC) smooth muscle cells were used. R899X(+/–) BMPR2 transgenic mice fed a Western diet for six weeks were given daily injections of IL-1ß prior to assessment for PAH and tissue collection. PASMC have reduced inflammatory activation in response to IL-1ß compared with AoSMCs; however, PASMC with reduced BMPR2 demonstrated an exaggerated response. Mice treated with IL-1ß had higher white blood cell counts and significantly raised serum protein levels of IL-6 and osteoprotegerin (OPG) plasma levels recapitulating in vitro data. Phenotypically, IL-1ß treated mice demonstrated increased pulmonary vascular remodeling. IL-1ß induces an exaggerated pulmonary artery specific transcriptomic inflammatory response when BMPR2 signaling is reduced. SAGE Publications 2017-09-22 /pmc/articles/PMC5703124/ /pubmed/28828907 http://dx.doi.org/10.1177/2045893217729096 Text en © The Author(s) 2017 http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution 4.0 License (http://www.creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Research Articles
Pickworth, Josephine
Rothman, Alexander
Iremonger, James
Casbolt, Helen
Hopkinson, Kay
Hickey, Peter M.
Gladson, Santhi
Shay, Sheila
Morrell, Nicholas W.
Francis, Sheila E.
West, James D.
Lawrie, Allan
Differential IL-1 signaling induced by BMPR2 deficiency drives pulmonary vascular remodeling
title Differential IL-1 signaling induced by BMPR2 deficiency drives pulmonary vascular remodeling
title_full Differential IL-1 signaling induced by BMPR2 deficiency drives pulmonary vascular remodeling
title_fullStr Differential IL-1 signaling induced by BMPR2 deficiency drives pulmonary vascular remodeling
title_full_unstemmed Differential IL-1 signaling induced by BMPR2 deficiency drives pulmonary vascular remodeling
title_short Differential IL-1 signaling induced by BMPR2 deficiency drives pulmonary vascular remodeling
title_sort differential il-1 signaling induced by bmpr2 deficiency drives pulmonary vascular remodeling
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703124/
https://www.ncbi.nlm.nih.gov/pubmed/28828907
http://dx.doi.org/10.1177/2045893217729096
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