Defective Glyoxalase 1 Contributes to Pathogenic Inflammation in Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive disorder that affects multiple organs, although a decline in respiratory function represents the major cause of morbidity and mortality. The airways of CF patients are characterized by a chronic inflammatory state to which the receptor for advanced glyc...

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Autores principales:	Marilena Pariano, Claudio Costantini, Ilaria Santarelli, Matteo Puccetti, Stefano Giovagnoli, Vincenzo N. Talesa, Luigina Romani, Cinzia Antognelli
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	glyoxalase 1 cystic fibrosis anakinra Medicine R
Acceso en línea:	https://doaj.org/article/f9fe7d53458f49b39fa7658da4c0e0ac
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spelling	oai:doaj.org-article:f9fe7d53458f49b39fa7658da4c0e0ac2021-11-25T19:11:14ZDefective Glyoxalase 1 Contributes to Pathogenic Inflammation in Cystic Fibrosis10.3390/vaccines91113112076-393Xhttps://doaj.org/article/f9fe7d53458f49b39fa7658da4c0e0ac2021-11-01T00:00:00Zhttps://www.mdpi.com/2076-393X/9/11/1311https://doaj.org/toc/2076-393XCystic fibrosis (CF) is an autosomal recessive disorder that affects multiple organs, although a decline in respiratory function represents the major cause of morbidity and mortality. The airways of CF patients are characterized by a chronic inflammatory state to which the receptor for advanced glycation end-products greatly contributes. Glyoxalase 1 (GLO1) is the major enzyme metabolizing methylglyoxal, a potent precursor of advanced glycation end-products. Its role in CF has never been investigated. We herein resorted to murine and human preclinical models of CF to define the contribution of GLO1 to inflammatory pathology. We found that the expression and activity of GLO1, measured by real-time PCR and Western blot or a specific spectrophotometric assay, respectively, are defective in mice and human bronchial cells from CF patients exposed to <i>Aspergillus fumigatus</i>, a common pathogen in CF, but could be restored upon blockade of interleukin-1 receptor signaling by anakinra in mice. This study suggests that GLO1 contributes to pathology in CF and may be potentially targeted to mitigate inflammation.Marilena ParianoClaudio CostantiniIlaria SantarelliMatteo PuccettiStefano GiovagnoliVincenzo N. TalesaLuigina RomaniCinzia AntognelliMDPI AGarticleglyoxalase 1cystic fibrosisanakinraMedicineRENVaccines, Vol 9, Iss 1311, p 1311 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glyoxalase 1 cystic fibrosis anakinra Medicine R
spellingShingle	glyoxalase 1 cystic fibrosis anakinra Medicine R Marilena Pariano Claudio Costantini Ilaria Santarelli Matteo Puccetti Stefano Giovagnoli Vincenzo N. Talesa Luigina Romani Cinzia Antognelli Defective Glyoxalase 1 Contributes to Pathogenic Inflammation in Cystic Fibrosis
description	Cystic fibrosis (CF) is an autosomal recessive disorder that affects multiple organs, although a decline in respiratory function represents the major cause of morbidity and mortality. The airways of CF patients are characterized by a chronic inflammatory state to which the receptor for advanced glycation end-products greatly contributes. Glyoxalase 1 (GLO1) is the major enzyme metabolizing methylglyoxal, a potent precursor of advanced glycation end-products. Its role in CF has never been investigated. We herein resorted to murine and human preclinical models of CF to define the contribution of GLO1 to inflammatory pathology. We found that the expression and activity of GLO1, measured by real-time PCR and Western blot or a specific spectrophotometric assay, respectively, are defective in mice and human bronchial cells from CF patients exposed to <i>Aspergillus fumigatus</i>, a common pathogen in CF, but could be restored upon blockade of interleukin-1 receptor signaling by anakinra in mice. This study suggests that GLO1 contributes to pathology in CF and may be potentially targeted to mitigate inflammation.
format	article
author	Marilena Pariano Claudio Costantini Ilaria Santarelli Matteo Puccetti Stefano Giovagnoli Vincenzo N. Talesa Luigina Romani Cinzia Antognelli
author_facet	Marilena Pariano Claudio Costantini Ilaria Santarelli Matteo Puccetti Stefano Giovagnoli Vincenzo N. Talesa Luigina Romani Cinzia Antognelli
author_sort	Marilena Pariano
title	Defective Glyoxalase 1 Contributes to Pathogenic Inflammation in Cystic Fibrosis
title_short	Defective Glyoxalase 1 Contributes to Pathogenic Inflammation in Cystic Fibrosis
title_full	Defective Glyoxalase 1 Contributes to Pathogenic Inflammation in Cystic Fibrosis
title_fullStr	Defective Glyoxalase 1 Contributes to Pathogenic Inflammation in Cystic Fibrosis
title_full_unstemmed	Defective Glyoxalase 1 Contributes to Pathogenic Inflammation in Cystic Fibrosis
title_sort	defective glyoxalase 1 contributes to pathogenic inflammation in cystic fibrosis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f9fe7d53458f49b39fa7658da4c0e0ac
work_keys_str_mv	AT marilenapariano defectiveglyoxalase1contributestopathogenicinflammationincysticfibrosis AT claudiocostantini defectiveglyoxalase1contributestopathogenicinflammationincysticfibrosis AT ilariasantarelli defectiveglyoxalase1contributestopathogenicinflammationincysticfibrosis AT matteopuccetti defectiveglyoxalase1contributestopathogenicinflammationincysticfibrosis AT stefanogiovagnoli defectiveglyoxalase1contributestopathogenicinflammationincysticfibrosis AT vincenzontalesa defectiveglyoxalase1contributestopathogenicinflammationincysticfibrosis AT luiginaromani defectiveglyoxalase1contributestopathogenicinflammationincysticfibrosis AT cinziaantognelli defectiveglyoxalase1contributestopathogenicinflammationincysticfibrosis
_version_	1718410255706095616

Defective Glyoxalase 1 Contributes to Pathogenic Inflammation in Cystic Fibrosis

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