{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:12:15Z","timestamp":1785841935442,"version":"3.56.0"},"reference-count":72,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU H2020 contract HarmonicSS","award":["H2020-SC1-2016-RTD\/731944"],"award-info":[{"award-number":["H2020-SC1-2016-RTD\/731944"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In primary Sj\u00f6gren\u2019s syndrome (pSS) patients, salivary gland (SG) epithelial cells (SGECs) could be exposed to chronic hyperosmotic stress (HOS), consecutive to their destruction and deregulation, that exacerbates an inflammatory response. The aims of this study were to assess the mechanism accounting for C-C motif chemokine ligand 2 (CCL2) expression in an immortalized human salivary gland epithelial acinar cell line (NS-SV-AC) subjected to HOS, as well as the involvement of CCL2 in pSS. CCL2 mRNA and protein levels were determined via RT-qPCR and ELISA. Reporter plasmids and a promoter pull-down assay were used to identify transcription factors associated with CCL2 mRNA increase. Our data showed that HOS-induced CCL2 mRNA increase was independent of the nuclear factor of activated T-cells 5 (NFAT5) and nuclear factor-kappa B (NFkB) but involved Kruppel-like factor 5 (KLF5). CCL2 protein levels, quantified by enzyme-linked immunosorbent assay (ELISA) in sera samples from pSS patients, correlated with the European Alliance of Associations for Rheumatology\u2019s Sjogren\u2019s syndrome disease activity index (ESSDAI) score for systemic activity. In addition, CCL2 protein levels were higher in patients with biological activity, cutaneous manifestations, and ESSDAI score superior or equal to five. Our data suggest that chronic HOS could exacerbate pSS disease by contributing to the inflammatory process induced by the expression and secretion of CCL2.<\/jats:p>","DOI":"10.3390\/ijms25020915","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T06:52:14Z","timestamp":1704955934000},"page":"915","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Involvement of CCL2 in Salivary Gland Response to Hyperosmolar Stress Related to Sj\u00f6gren\u2019s Syndrome"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3038-8988","authenticated-orcid":false,"given":"Clara","family":"Chivasso","sequence":"first","affiliation":[{"name":"Laboratory of Pathophysiological and Nutritional Biochemistry, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorian","family":"Parisis","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiological and Nutritional Biochemistry, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"},{"name":"Department of Rheumatology, The Brussels University Hospital\u2014Erasme Hospital, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Cabrol","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The Brussels University Hospital\u2014Erasme Hospital, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0049-9983","authenticated-orcid":false,"given":"Azine","family":"Datlibagi","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiological and Nutritional Biochemistry, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Delforge","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiological and Nutritional Biochemistry, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Gregoire","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiological and Nutritional Biochemistry, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nargis","family":"Bolaky","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiological and Nutritional Biochemistry, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Shahnawaz","family":"Soyfoo","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The Brussels University Hospital\u2014Erasme Hospital, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7161-7604","authenticated-orcid":false,"given":"Jason","family":"Perret","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiological and Nutritional Biochemistry, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0385-5824","authenticated-orcid":false,"given":"Christine","family":"Delporte","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiological and Nutritional Biochemistry, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.medcli.2022.10.007","article-title":"Sj\u00f6gren Syndrome","volume":"160","author":"Retamozo","year":"2023","journal-title":"Med. 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