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...
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| Format: | Article |
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Nature Portfolio
2017-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-09309-8 |
| _version_ | 1818841144104058880 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T04:21:24Z |
| format | Article |
| id | doaj.art-cf83dcd2d2174c98a2b3b74f31393df9 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:21:24Z |
| publishDate | 2017-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-cf83dcd2d2174c98a2b3b74f31393df92022-12-21T20:36:08ZengNature PortfolioScientific Reports2045-23222017-08-01711910.1038/s41598-017-09309-8Hypoxia triggers IFN-I production in muscle: Implications in dermatomyositisNoemí De Luna0Xavier Suárez-Calvet1Cinta Lleixà2Jordi Diaz-Manera3Montse Olivé4Isabel Illa5Eduard Gallardo6Neuromuscular Diseases Unit, Neurology Department, Hospital de la Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Institut de Recerca Sant Pau, (Barcelona) and Biomedical Network Research Centre on Rare Diseases (CIBERER)Neuromuscular Diseases Unit, Neurology Department, Hospital de la Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Institut de Recerca Sant Pau, (Barcelona) and Biomedical Network Research Centre on Rare Diseases (CIBERER)Neuromuscular Diseases Unit, Neurology Department, Hospital de la Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Institut de Recerca Sant Pau, (Barcelona) and Biomedical Network Research Centre on Rare Diseases (CIBERER)Neuromuscular Diseases Unit, Neurology Department, Hospital de la Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Institut de Recerca Sant Pau, (Barcelona) and Biomedical Network Research Centre on Rare Diseases (CIBERER)Department of Pathology and Neuromuscular Unit, IDIBELL-Hospital Universitari de BellvitgeNeuromuscular Diseases Unit, Neurology Department, Hospital de la Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Institut de Recerca Sant Pau, (Barcelona) and Biomedical Network Research Centre on Rare Diseases (CIBERER)Neuromuscular Diseases Unit, Neurology Department, Hospital de la Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Institut de Recerca Sant Pau, (Barcelona) and Biomedical Network Research Centre on Rare Diseases (CIBERER)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.https://doi.org/10.1038/s41598-017-09309-8 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | Hypoxia triggers IFN-I production in muscle: Implications in dermatomyositis |
| title_sort | hypoxia triggers ifn i production in muscle implications in dermatomyositis |
| url | https://doi.org/10.1038/s41598-017-09309-8 |
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