JAK Inhibitors and Oxidative Stress Control
Primary Sjögren's syndrome (SjS) is a complex autoimmune epithelitis, with few treatment options, but the use of Janus kinase (JAK) inhibitors is promising because suppression of the JAK/signal transducer and activator of transcription (STAT) pathway improves sicca manifestations. Playing a pri...
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doaj-f3f59f2d44c541e3a02494d7047f96612020-11-25T02:05:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-12-011010.3389/fimmu.2019.02814471686JAK Inhibitors and Oxidative Stress ControlAmandine Charras0Pinelopi Arvaniti1Pinelopi Arvaniti2Pinelopi Arvaniti3Christelle Le Dantec4George N. Dalekos5George N. Dalekos6Kaliopi Zachou7Kaliopi Zachou8Anne Bordron9Yves Renaudineau10Yves Renaudineau11UMR1227, Lymphocytes B et Autoimmunité, Université de Brest, INSERM, CHU de Brest, Brest, FranceLaboratory of Immunology and Immunotherapy, Brest University Medical School Hospital, Brest, FranceInstitute of Internal Medicine and Hepatology, Larissa, GreeceDepartment of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, Larissa, GreeceUMR1227, Lymphocytes B et Autoimmunité, Université de Brest, INSERM, CHU de Brest, Brest, FranceInstitute of Internal Medicine and Hepatology, Larissa, GreeceDepartment of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, Larissa, GreeceInstitute of Internal Medicine and Hepatology, Larissa, GreeceDepartment of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, Larissa, GreeceUMR1227, Lymphocytes B et Autoimmunité, Université de Brest, INSERM, CHU de Brest, Brest, FranceUMR1227, Lymphocytes B et Autoimmunité, Université de Brest, INSERM, CHU de Brest, Brest, FranceLaboratory of Immunology and Immunotherapy, Brest University Medical School Hospital, Brest, FrancePrimary Sjögren's syndrome (SjS) is a complex autoimmune epithelitis, with few treatment options, but the use of Janus kinase (JAK) inhibitors is promising because suppression of the JAK/signal transducer and activator of transcription (STAT) pathway improves sicca manifestations. Playing a primary and pathogenic role in disease development, the oxidative stress response is upregulated in activated salivary gland epithelial cells (SGECs) from patients with SjS. Therefore, the aim of this study was to investigate whether JAK inhibitors would suppress SGEC activation in response to an oxidative stress. For this purpose, the human salivary gland (HSG) cell line was used, and cells were treated with the reactive oxygen species (ROS) inducer hydrogen peroxide (H2O2) or with interferons (IFN Type I and Type II), used as positive controls, to mimic activated SGECs as observed in SjS patients. Afterward, the levels of the intracellular adhesion molecule-1 (ICAM-1) and the regulatory programmed-death ligand-1 (PD-L1) were measured by real-time PCR and flow cytometry, and the STAT1/3 phosphorylation status was assessed by Western blotting. Using the HSG cell line, our results showed that both ICAM-1 and PD-L1 are induced by ROS through pSTAT3, and that this activation pathway is reversed by the use of JAK inhibitors, AG490 and ruxolitinib, as well as by N-acetylcysteine, which is a direct inhibitor of ROS. These findings open new perspectives regarding the pathogenesis and therapeutic possibilities for SjS.https://www.frontiersin.org/article/10.3389/fimmu.2019.02814/fullprimary sjögren's syndromeROSJAK/STAT pathwayICAM-1PD-L1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Amandine Charras Pinelopi Arvaniti Pinelopi Arvaniti Pinelopi Arvaniti Christelle Le Dantec George N. Dalekos George N. Dalekos Kaliopi Zachou Kaliopi Zachou Anne Bordron Yves Renaudineau Yves Renaudineau |
spellingShingle |
Amandine Charras Pinelopi Arvaniti Pinelopi Arvaniti Pinelopi Arvaniti Christelle Le Dantec George N. Dalekos George N. Dalekos Kaliopi Zachou Kaliopi Zachou Anne Bordron Yves Renaudineau Yves Renaudineau JAK Inhibitors and Oxidative Stress Control Frontiers in Immunology primary sjögren's syndrome ROS JAK/STAT pathway ICAM-1 PD-L1 |
author_facet |
Amandine Charras Pinelopi Arvaniti Pinelopi Arvaniti Pinelopi Arvaniti Christelle Le Dantec George N. Dalekos George N. Dalekos Kaliopi Zachou Kaliopi Zachou Anne Bordron Yves Renaudineau Yves Renaudineau |
author_sort |
Amandine Charras |
title |
JAK Inhibitors and Oxidative Stress Control |
title_short |
JAK Inhibitors and Oxidative Stress Control |
title_full |
JAK Inhibitors and Oxidative Stress Control |
title_fullStr |
JAK Inhibitors and Oxidative Stress Control |
title_full_unstemmed |
JAK Inhibitors and Oxidative Stress Control |
title_sort |
jak inhibitors and oxidative stress control |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-12-01 |
description |
Primary Sjögren's syndrome (SjS) is a complex autoimmune epithelitis, with few treatment options, but the use of Janus kinase (JAK) inhibitors is promising because suppression of the JAK/signal transducer and activator of transcription (STAT) pathway improves sicca manifestations. Playing a primary and pathogenic role in disease development, the oxidative stress response is upregulated in activated salivary gland epithelial cells (SGECs) from patients with SjS. Therefore, the aim of this study was to investigate whether JAK inhibitors would suppress SGEC activation in response to an oxidative stress. For this purpose, the human salivary gland (HSG) cell line was used, and cells were treated with the reactive oxygen species (ROS) inducer hydrogen peroxide (H2O2) or with interferons (IFN Type I and Type II), used as positive controls, to mimic activated SGECs as observed in SjS patients. Afterward, the levels of the intracellular adhesion molecule-1 (ICAM-1) and the regulatory programmed-death ligand-1 (PD-L1) were measured by real-time PCR and flow cytometry, and the STAT1/3 phosphorylation status was assessed by Western blotting. Using the HSG cell line, our results showed that both ICAM-1 and PD-L1 are induced by ROS through pSTAT3, and that this activation pathway is reversed by the use of JAK inhibitors, AG490 and ruxolitinib, as well as by N-acetylcysteine, which is a direct inhibitor of ROS. These findings open new perspectives regarding the pathogenesis and therapeutic possibilities for SjS. |
topic |
primary sjögren's syndrome ROS JAK/STAT pathway ICAM-1 PD-L1 |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.02814/full |
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