Pro-Inflammatory Properties of Salivary Gland-Derived Fibroblasts—Implications in Sjögren’s Disease
Salivary gland dysfunction is a hallmark of Sjögren’s disease (SjD). Here, we investigated the pro-inflammatory properties of salivary gland-derived fibroblasts (SGF) that were cultured from minor salivary gland (MSG) tissues of patients with SjD and controls. SGF from patients with SjD exhibited hi...
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MDPI AG
2025-04-01
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| author | Matthias Brunner Daniel Guggisberg Marco Sprecher Ondrej Pastva Kristina Bürki Miranda Houtman Marco Kreuzer Sara Andrea Krättli Laura Jahnke Mila Roceri Rémy Bruggmann Muriel Elhai Britta Maurer Thomas M. Marti Caroline Ospelt Kerstin Klein |
| author_facet | Matthias Brunner Daniel Guggisberg Marco Sprecher Ondrej Pastva Kristina Bürki Miranda Houtman Marco Kreuzer Sara Andrea Krättli Laura Jahnke Mila Roceri Rémy Bruggmann Muriel Elhai Britta Maurer Thomas M. Marti Caroline Ospelt Kerstin Klein |
| author_sort | Matthias Brunner |
| collection | DOAJ |
| description | Salivary gland dysfunction is a hallmark of Sjögren’s disease (SjD). Here, we investigated the pro-inflammatory properties of salivary gland-derived fibroblasts (SGF) that were cultured from minor salivary gland (MSG) tissues of patients with SjD and controls. SGF from patients with SjD exhibited higher rates of proliferation compared to controls. RNA sequencing revealed pronounced pro-inflammatory properties of SGF in response to stimulation with IL1 and polyI:C, with an activation of “interferon responses”, “JAK STAT”, and “NF-kappa B” signaling, as well as ”complement” pathways. In addition to encoding pro-inflammatory transcripts, stimulated SGF featured increased expression of a number of non-coding enhancer RNAs (eRNAs) that we originally identified in TNF-stimulated synovial fibroblasts (FLS) by CAGE sequencing. We confirmed the expression of selected eRNAs in SGF and FLS through time-course experiments upon stimulation with different pro-inflammatory stimuli using real-time PCR. Furthermore, we detected eRNAs for IL6 (eIL6) and IL8 (eIL8#3) in MSG tissues. Treatment of SGF with the bromodomain inhibitor I-BET suppressed IL1- and LPS-induced expression of all eRNAs tested, as well as their associated pro-inflammatory coding transcripts. Transfection of SGF with antisense nucleotides targeting eCCL20 reduced the LPS-induced expression of this eRNA, as well as CCL20 expression and secretion. Together, our data highlight similarities between SGF and FLS regarding their activation under inflammatory conditions. |
| format | Article |
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| issn | 2073-4409 |
| language | English |
| publishDate | 2025-04-01 |
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| series | Cells |
| spelling | doaj-art-7daba7064e444d12afb70581207b25712025-08-20T02:17:20ZengMDPI AGCells2073-44092025-04-0114855810.3390/cells14080558Pro-Inflammatory Properties of Salivary Gland-Derived Fibroblasts—Implications in Sjögren’s DiseaseMatthias Brunner0Daniel Guggisberg1Marco Sprecher2Ondrej Pastva3Kristina Bürki4Miranda Houtman5Marco Kreuzer6Sara Andrea Krättli7Laura Jahnke8Mila Roceri9Rémy Bruggmann10Muriel Elhai11Britta Maurer12Thomas M. Marti13Caroline Ospelt14Kerstin Klein15Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, 3008 Bern, SwitzerlandDepartment of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, 3008 Bern, SwitzerlandDepartment of Rheumatology, University Hospital Zurich, University of Zurich, 8091 Zurich, SwitzerlandLung Precision Medicine (LPM), Department for BioMedical Research, 3008 Bern, SwitzerlandDepartment of Rheumatology, University Hospital Zurich, University of Zurich, 8091 Zurich, SwitzerlandDepartment of Rheumatology, University Hospital Zurich, University of Zurich, 8091 Zurich, SwitzerlandInterfaculty Bioinformatics Unit, University of Bern, 3012 Bern, SwitzerlandInterfaculty Bioinformatics Unit, University of Bern, 3012 Bern, SwitzerlandLung Precision Medicine (LPM), Department for BioMedical Research, 3008 Bern, SwitzerlandDepartment of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, 3008 Bern, SwitzerlandInterfaculty Bioinformatics Unit, University of Bern, 3012 Bern, SwitzerlandDepartment of Rheumatology, University Hospital Zurich, University of Zurich, 8091 Zurich, SwitzerlandDepartment of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, 3008 Bern, SwitzerlandLung Precision Medicine (LPM), Department for BioMedical Research, 3008 Bern, SwitzerlandDepartment of Rheumatology, University Hospital Zurich, University of Zurich, 8091 Zurich, SwitzerlandDepartment of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, 3008 Bern, SwitzerlandSalivary gland dysfunction is a hallmark of Sjögren’s disease (SjD). Here, we investigated the pro-inflammatory properties of salivary gland-derived fibroblasts (SGF) that were cultured from minor salivary gland (MSG) tissues of patients with SjD and controls. SGF from patients with SjD exhibited higher rates of proliferation compared to controls. RNA sequencing revealed pronounced pro-inflammatory properties of SGF in response to stimulation with IL1 and polyI:C, with an activation of “interferon responses”, “JAK STAT”, and “NF-kappa B” signaling, as well as ”complement” pathways. In addition to encoding pro-inflammatory transcripts, stimulated SGF featured increased expression of a number of non-coding enhancer RNAs (eRNAs) that we originally identified in TNF-stimulated synovial fibroblasts (FLS) by CAGE sequencing. We confirmed the expression of selected eRNAs in SGF and FLS through time-course experiments upon stimulation with different pro-inflammatory stimuli using real-time PCR. Furthermore, we detected eRNAs for IL6 (eIL6) and IL8 (eIL8#3) in MSG tissues. Treatment of SGF with the bromodomain inhibitor I-BET suppressed IL1- and LPS-induced expression of all eRNAs tested, as well as their associated pro-inflammatory coding transcripts. Transfection of SGF with antisense nucleotides targeting eCCL20 reduced the LPS-induced expression of this eRNA, as well as CCL20 expression and secretion. Together, our data highlight similarities between SGF and FLS regarding their activation under inflammatory conditions.https://www.mdpi.com/2073-4409/14/8/558Sjögren’s diseasesalivary glandinflammationfibroblastenhancerbromodomain |
| spellingShingle | Matthias Brunner Daniel Guggisberg Marco Sprecher Ondrej Pastva Kristina Bürki Miranda Houtman Marco Kreuzer Sara Andrea Krättli Laura Jahnke Mila Roceri Rémy Bruggmann Muriel Elhai Britta Maurer Thomas M. Marti Caroline Ospelt Kerstin Klein Pro-Inflammatory Properties of Salivary Gland-Derived Fibroblasts—Implications in Sjögren’s Disease Cells Sjögren’s disease salivary gland inflammation fibroblast enhancer bromodomain |
| title | Pro-Inflammatory Properties of Salivary Gland-Derived Fibroblasts—Implications in Sjögren’s Disease |
| title_full | Pro-Inflammatory Properties of Salivary Gland-Derived Fibroblasts—Implications in Sjögren’s Disease |
| title_fullStr | Pro-Inflammatory Properties of Salivary Gland-Derived Fibroblasts—Implications in Sjögren’s Disease |
| title_full_unstemmed | Pro-Inflammatory Properties of Salivary Gland-Derived Fibroblasts—Implications in Sjögren’s Disease |
| title_short | Pro-Inflammatory Properties of Salivary Gland-Derived Fibroblasts—Implications in Sjögren’s Disease |
| title_sort | pro inflammatory properties of salivary gland derived fibroblasts implications in sjogren s disease |
| topic | Sjögren’s disease salivary gland inflammation fibroblast enhancer bromodomain |
| url | https://www.mdpi.com/2073-4409/14/8/558 |
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