{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T20:49:28Z","timestamp":1784580568035,"version":"3.55.0"},"reference-count":31,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"an Interdisciplinary grant of the University of Bern (UniBe ID grant)"},{"name":"The Swiss Life Jubil\u00e4umsstiftung"},{"name":"an SF Board call project grant of the medical faculty of the University of Ber"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Salivary gland dysfunction is a hallmark of Sj\u00f6gren\u2019s 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 \u201cinterferon responses\u201d, \u201cJAK STAT\u201d, and \u201cNF-kappa B\u201d signaling, as well as \u201dcomplement\u201d 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.<\/jats:p>","DOI":"10.3390\/cells14080558","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T12:05:56Z","timestamp":1744200356000},"page":"558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pro-Inflammatory Properties of Salivary Gland-Derived Fibroblasts\u2014Implications in Sj\u00f6gren\u2019s Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6781-6210","authenticated-orcid":false,"given":"Matthias","family":"Brunner","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, 3008 Bern, Switzerland"},{"name":"Lung Precision Medicine (LPM), Department for BioMedical Research, 3008 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Guggisberg","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, 3008 Bern, Switzerland"},{"name":"Lung Precision Medicine (LPM), Department for BioMedical Research, 3008 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Sprecher","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-3584","authenticated-orcid":false,"given":"Ondrej","family":"Pastva","sequence":"additional","affiliation":[{"name":"Lung Precision Medicine (LPM), Department for BioMedical Research, 3008 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"B\u00fcrki","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5317-0327","authenticated-orcid":false,"given":"Miranda","family":"Houtman","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6784-0854","authenticated-orcid":false,"given":"Marco","family":"Kreuzer","sequence":"additional","affiliation":[{"name":"Interfaculty Bioinformatics Unit, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4679-3112","authenticated-orcid":false,"given":"Sara Andrea","family":"Kr\u00e4ttli","sequence":"additional","affiliation":[{"name":"Interfaculty Bioinformatics Unit, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7762-5162","authenticated-orcid":false,"given":"Laura","family":"Jahnke","sequence":"additional","affiliation":[{"name":"Lung Precision Medicine (LPM), Department for BioMedical Research, 3008 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mila","family":"Roceri","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, 3008 Bern, Switzerland"},{"name":"Lung Precision Medicine (LPM), Department for BioMedical Research, 3008 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5629-6363","authenticated-orcid":false,"given":"R\u00e9my","family":"Bruggmann","sequence":"additional","affiliation":[{"name":"Interfaculty Bioinformatics Unit, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Elhai","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Maurer","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, 3008 Bern, Switzerland"},{"name":"Lung Precision Medicine (LPM), Department for BioMedical Research, 3008 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3005-220X","authenticated-orcid":false,"given":"Thomas M.","family":"Marti","sequence":"additional","affiliation":[{"name":"Lung Precision Medicine (LPM), Department for BioMedical Research, 3008 Bern, Switzerland"},{"name":"Department of General Thoracic Surgery, Inselspital, Bern University Hospital, 3008 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Ospelt","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5303-8027","authenticated-orcid":false,"given":"Kerstin","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, 3008 Bern, Switzerland"},{"name":"Lung Precision Medicine (LPM), Department for BioMedical Research, 3008 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1056\/NEJMcp1702514","article-title":"Primary Sjogren\u2019s Syndrome","volume":"378","author":"Mariette","year":"2018","journal-title":"N. 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