Sildenafil Counteracts the In Vitro Activation of CXCL-9, CXCL-10 and CXCL-11/CXCR3 Axis Induced by Reactive Oxygen Species in Scleroderma Fibroblasts
Oxidative stress plays a key role in systemic sclerosis (SSc) pathogenesis, and an altered redox homeostasis might be responsible for abnormal inflammatory status, fibrosis and tissue damage extension. In this study, we explored the effect of the phosphodiesterase type 5 inhibitor sildenafil in modu...
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MDPI AG
2021-05-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/10/6/491 |
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| author | Cristina Antinozzi Paolo Sgrò Francesco Marampon Daniela Caporossi Francesco Del Galdo Ivan Dimauro Luigi Di Luigi |
| author_facet | Cristina Antinozzi Paolo Sgrò Francesco Marampon Daniela Caporossi Francesco Del Galdo Ivan Dimauro Luigi Di Luigi |
| author_sort | Cristina Antinozzi |
| collection | DOAJ |
| description | Oxidative stress plays a key role in systemic sclerosis (SSc) pathogenesis, and an altered redox homeostasis might be responsible for abnormal inflammatory status, fibrosis and tissue damage extension. In this study, we explored the effect of the phosphodiesterase type 5 inhibitor sildenafil in modulating the activation of the CXCL-9, -10, -11/CXCR3 axis, which is fundamental in the perpetuation of inflammation in different autoimmune diseases, in the cell culture of SSc human dermal fibroblasts exposed to a pro-oxidant environment. We observed that sildenafil significantly reduced gene expression and release of CXCL-9, -10 and -11, inhibited the CXCR3 action and suppressed the activation of STAT1-, JNK- and p38MAPK pathways. This in vitro study on dermal fibroblasts supports clinical studies to consider the efficacy of sildenafil in preventing tissue damage and fibrosis in SSc by targeting central biomarkers of disease progression, vascular injuries and fibrosis and reducing the pro-inflammatory activation induced by oxidative stress. |
| first_indexed | 2024-03-10T10:49:58Z |
| format | Article |
| id | doaj.art-9b931e5816954fe0ac472e00d42eafc4 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T10:49:58Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-9b931e5816954fe0ac472e00d42eafc42023-11-21T22:18:35ZengMDPI AGBiology2079-77372021-05-0110649110.3390/biology10060491Sildenafil Counteracts the In Vitro Activation of CXCL-9, CXCL-10 and CXCL-11/CXCR3 Axis Induced by Reactive Oxygen Species in Scleroderma FibroblastsCristina Antinozzi0Paolo Sgrò1Francesco Marampon2Daniela Caporossi3Francesco Del Galdo4Ivan Dimauro5Luigi Di Luigi6Unit of Endocrinology, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, 00135 Rome, ItalyUnit of Endocrinology, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, 00135 Rome, ItalyUnit of Endocrinology, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, 00135 Rome, ItalyUnit of Biology and Genetic, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, 00135 Rome, ItalyLeeds Institue of Rheumatic and Musculoskeletal Medicine and Diseases and NIHR Biomedical Research Centre, University of Leeds, Leeds LS2 9JT, UKUnit of Biology and Genetic, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, 00135 Rome, ItalyUnit of Endocrinology, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, 00135 Rome, ItalyOxidative stress plays a key role in systemic sclerosis (SSc) pathogenesis, and an altered redox homeostasis might be responsible for abnormal inflammatory status, fibrosis and tissue damage extension. In this study, we explored the effect of the phosphodiesterase type 5 inhibitor sildenafil in modulating the activation of the CXCL-9, -10, -11/CXCR3 axis, which is fundamental in the perpetuation of inflammation in different autoimmune diseases, in the cell culture of SSc human dermal fibroblasts exposed to a pro-oxidant environment. We observed that sildenafil significantly reduced gene expression and release of CXCL-9, -10 and -11, inhibited the CXCR3 action and suppressed the activation of STAT1-, JNK- and p38MAPK pathways. This in vitro study on dermal fibroblasts supports clinical studies to consider the efficacy of sildenafil in preventing tissue damage and fibrosis in SSc by targeting central biomarkers of disease progression, vascular injuries and fibrosis and reducing the pro-inflammatory activation induced by oxidative stress.https://www.mdpi.com/2079-7737/10/6/491chemokinessystemic sclerosisreactive oxygen speciesfibrosissildenafil |
| spellingShingle | Cristina Antinozzi Paolo Sgrò Francesco Marampon Daniela Caporossi Francesco Del Galdo Ivan Dimauro Luigi Di Luigi Sildenafil Counteracts the In Vitro Activation of CXCL-9, CXCL-10 and CXCL-11/CXCR3 Axis Induced by Reactive Oxygen Species in Scleroderma Fibroblasts Biology chemokines systemic sclerosis reactive oxygen species fibrosis sildenafil |
| title | Sildenafil Counteracts the In Vitro Activation of CXCL-9, CXCL-10 and CXCL-11/CXCR3 Axis Induced by Reactive Oxygen Species in Scleroderma Fibroblasts |
| title_full | Sildenafil Counteracts the In Vitro Activation of CXCL-9, CXCL-10 and CXCL-11/CXCR3 Axis Induced by Reactive Oxygen Species in Scleroderma Fibroblasts |
| title_fullStr | Sildenafil Counteracts the In Vitro Activation of CXCL-9, CXCL-10 and CXCL-11/CXCR3 Axis Induced by Reactive Oxygen Species in Scleroderma Fibroblasts |
| title_full_unstemmed | Sildenafil Counteracts the In Vitro Activation of CXCL-9, CXCL-10 and CXCL-11/CXCR3 Axis Induced by Reactive Oxygen Species in Scleroderma Fibroblasts |
| title_short | Sildenafil Counteracts the In Vitro Activation of CXCL-9, CXCL-10 and CXCL-11/CXCR3 Axis Induced by Reactive Oxygen Species in Scleroderma Fibroblasts |
| title_sort | sildenafil counteracts the in vitro activation of cxcl 9 cxcl 10 and cxcl 11 cxcr3 axis induced by reactive oxygen species in scleroderma fibroblasts |
| topic | chemokines systemic sclerosis reactive oxygen species fibrosis sildenafil |
| url | https://www.mdpi.com/2079-7737/10/6/491 |
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