Hypoxia triggers IFN-I production in muscle: Implications in dermatomyositis

Abstract Dermatomyositis is an inflammatory myopathy characterized by symmetrical proximal muscle weakness and skin changes. Muscle biopsy hallmarks include perifascicular atrophy, loss of intramuscular capillaries, perivascular and perimysial inflammation and the overexpression of IFN-inducible gen...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Noemí De Luna, Xavier Suárez-Calvet, Cinta Lleixà, Jordi Diaz-Manera, Montse Olivé, Isabel Illa, Eduard Gallardo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cf83dcd2d2174c98a2b3b74f31393df9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:cf83dcd2d2174c98a2b3b74f31393df9
record_format	dspace
spelling	oai:doaj.org-article:cf83dcd2d2174c98a2b3b74f31393df92021-12-02T16:06:38ZHypoxia triggers IFN-I production in muscle: Implications in dermatomyositis10.1038/s41598-017-09309-82045-2322https://doaj.org/article/cf83dcd2d2174c98a2b3b74f31393df92017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09309-8https://doaj.org/toc/2045-2322Abstract Dermatomyositis is an inflammatory myopathy characterized by symmetrical proximal muscle weakness and skin changes. Muscle biopsy hallmarks include perifascicular atrophy, loss of intramuscular capillaries, perivascular and perimysial inflammation and the overexpression of IFN-inducible genes. Among them, the retinoic-acid inducible gene 1 (RIG-I) is specifically overexpressed in perifascicular areas of dermatomyositis muscle. The aim of this work was to study if RIG-I expression may be modulated by hypoxia using an in vitro approach. We identified putative hypoxia response elements (HRE) in RIG-I regulatory regions and luciferase assays confirmed that RIG-I is a new HIF-inducible gene. We observed an increase expression of RIG-I both by Real time PCR and Western blot in hypoxic conditions in human muscle cells. Cell transfection with a constitutive RIG-I expression vector increased levels of phospho-IRF-3, indicating that RIG-I promotes binding of transcription factors to the enhancer sequence of IFN. Moreover, release of IFN-β was observed in hypoxic conditions. Finally, HIF-1α overexpression was confirmed in the muscle biopsies and in some RIG-I positive perifascicular muscle fibres but not in controls. Our results indicate that hypoxia triggers the production of IFN-I in vitro, and may contribute to the pathogenesis of DM together with other inflammatory factors.Noemí De LunaXavier Suárez-CalvetCinta LleixàJordi Diaz-ManeraMontse OlivéIsabel IllaEduard GallardoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Noemí De Luna Xavier Suárez-Calvet Cinta Lleixà Jordi Diaz-Manera Montse Olivé Isabel Illa Eduard Gallardo Hypoxia triggers IFN-I production in muscle: Implications in dermatomyositis
description	Abstract Dermatomyositis is an inflammatory myopathy characterized by symmetrical proximal muscle weakness and skin changes. Muscle biopsy hallmarks include perifascicular atrophy, loss of intramuscular capillaries, perivascular and perimysial inflammation and the overexpression of IFN-inducible genes. Among them, the retinoic-acid inducible gene 1 (RIG-I) is specifically overexpressed in perifascicular areas of dermatomyositis muscle. The aim of this work was to study if RIG-I expression may be modulated by hypoxia using an in vitro approach. We identified putative hypoxia response elements (HRE) in RIG-I regulatory regions and luciferase assays confirmed that RIG-I is a new HIF-inducible gene. We observed an increase expression of RIG-I both by Real time PCR and Western blot in hypoxic conditions in human muscle cells. Cell transfection with a constitutive RIG-I expression vector increased levels of phospho-IRF-3, indicating that RIG-I promotes binding of transcription factors to the enhancer sequence of IFN. Moreover, release of IFN-β was observed in hypoxic conditions. Finally, HIF-1α overexpression was confirmed in the muscle biopsies and in some RIG-I positive perifascicular muscle fibres but not in controls. Our results indicate that hypoxia triggers the production of IFN-I in vitro, and may contribute to the pathogenesis of DM together with other inflammatory factors.
format	article
author	Noemí De Luna Xavier Suárez-Calvet Cinta Lleixà Jordi Diaz-Manera Montse Olivé Isabel Illa Eduard Gallardo
author_facet	Noemí De Luna Xavier Suárez-Calvet Cinta Lleixà Jordi Diaz-Manera Montse Olivé Isabel Illa Eduard Gallardo
author_sort	Noemí De Luna
title	Hypoxia triggers IFN-I production in muscle: Implications in dermatomyositis
title_short	Hypoxia triggers IFN-I production in muscle: Implications in dermatomyositis
title_full	Hypoxia triggers IFN-I production in muscle: Implications in dermatomyositis
title_fullStr	Hypoxia triggers IFN-I production in muscle: Implications in dermatomyositis
title_full_unstemmed	Hypoxia triggers IFN-I production in muscle: Implications in dermatomyositis
title_sort	hypoxia triggers ifn-i production in muscle: implications in dermatomyositis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/cf83dcd2d2174c98a2b3b74f31393df9
work_keys_str_mv	AT noemideluna hypoxiatriggersifniproductioninmuscleimplicationsindermatomyositis AT xaviersuarezcalvet hypoxiatriggersifniproductioninmuscleimplicationsindermatomyositis AT cintalleixa hypoxiatriggersifniproductioninmuscleimplicationsindermatomyositis AT jordidiazmanera hypoxiatriggersifniproductioninmuscleimplicationsindermatomyositis AT montseolive hypoxiatriggersifniproductioninmuscleimplicationsindermatomyositis AT isabelilla hypoxiatriggersifniproductioninmuscleimplicationsindermatomyositis AT eduardgallardo hypoxiatriggersifniproductioninmuscleimplicationsindermatomyositis
_version_	1718384932974231552

Hypoxia triggers IFN-I production in muscle: Implications in dermatomyositis

Ejemplares similares