{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T21:19:49Z","timestamp":1783718389002,"version":"3.55.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":2093,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,4,20]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Sj\u00f6gren's syndrome (SS) is an autoimmune disease and the second most common chronic systemic rheumatic disorder. Prevalence of primary SS in the general population has been estimated to be approximately 1\u20133%, whereas secondary SS has been observed in 10\u201320% of patients with rheumatoid arthritis, systemic lupus erythematosus (SLE) and scleroderma. Despite this, its exact aetiology and pathogenesis are largely unexplored. Nuclear factor-kappa B (NF-\u03baB) signalling mechanisms provide central controls in SS, but how these pathways intersect the pathological features of this disease is unclear. The ubiquitin-editing enzyme A20 (tumour necrosis factor-\u03b1-induced protein 3, TNFAIP3) serves as a critical inhibitor on NF-\u03baB signalling. In humans, polymorphisms in the A20 gene or a deregulated expression of A20 are often associated with several inflammatory disorders, including SS. Because A20 controls the ectodysplasin-A1 (EDA-A1)\/ectodysplasin receptor (EDAR) signalling negatively, and the deletion of A20 results in excessive EDA1-induced NF-\u03baB signalling, this work investigates the expression levels of EDA-A1 and EDAR in SS human salivary glands epithelial cells (SGEC) and evaluates the hypothesis that SS SGEC-specific deregulation of A20 results in excessive EDA1-induced NF-\u03baB signalling in SS. Our approach, which combines the use of siRNA-mediated gene silencing and quantitative pathway analysis, was used to elucidate the role of the A20 target gene in intracellular EDA-A1\/EDAR\/NF-\u03baB pathway in SS SGEC, holding significant promise for compound selection in drug discovery.<\/jats:p>","DOI":"10.1111\/cei.12764","type":"journal-article","created":{"date-parts":[[2016,1,2]],"date-time":"2016-01-02T16:08:42Z","timestamp":1451750922000},"page":"183-196","source":"Crossref","is-referenced-by-count":18,"title":["Downstream activation of NF-\u03baB in the EDA-A1\/EDAR signalling in Sj\u00f6gren's syndrome and its regulation by the ubiquitin-editing enzyme A20"],"prefix":"10.1093","volume":"184","author":[{"given":"M","family":"Sisto","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Barca","sequence":"additional","affiliation":[{"name":"Neuropathology Unit, Institute of Experimental Neurology and Division of Neuroscience, IRCCS San Raffaele Scientific Institute (Section of Lecce), Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D D","family":"Lofrumento","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Lisi","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,2,23]]},"reference":[{"key":"2021111804091604600_cei12764-bib-0001","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0140-6736(05)66990-5","article-title":"Sjogren's syndrome","volume":"366","author":"Fox","year":"2005","journal-title":"Lancet"},{"key":"2021111804091604600_cei12764-bib-0002","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/S0962-8924(01)02064-5","article-title":"Signal transduction by tumor necrosis factor and its relatives","volume":"11","author":"Baud","year":"2001","journal-title":"Trends Cell Biol"},{"key":"2021111804091604600_cei12764-bib-0003","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S1357-4310(00)01814-1","article-title":"NF-kappaB as a therapeutic target in chronic inflammation: recent advances","volume":"6","author":"Makarov","year":"2000","journal-title":"Mol Med 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