{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T06:10:33Z","timestamp":1777529433285,"version":"3.51.4"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,12,18]],"date-time":"2017-12-18T00:00:00Z","timestamp":1513555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Salivary gland (SG) injurious agents are all translated into loss of salivation (xerostomia). An association has been established between activation of innate immunity and SG injury and dysfunction. However, it remains unclear how the secretory epithelia respond by halting saliva production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>C57BL\/6 submandibular glands (SMGs) were acutely challenged using a single dose of the innate immune stimulant: polyinosinic\u2010polycytidylic acid (poly (I:C)). Secretory capacity of the infected SMGs was substantiated by assessing the flow rate in response to pilocarpine stimulation. Depletion of the acute inflammatory cells was achieved by pre\u2010treating mice with RB6\u20108C5 depletion antibody. Flow cytometry, histology and immunohistochemistry were conducted to verify the immune cell depletion. Epithelial expression of saliva\u2010driving molecules: muscarinic 3 receptor (M3R), aquaporin 5 water channel (AQP5), Na\u2010K\u2010CL\u2010Cotransporter 1 (NKCC1) and transmembrane member 16A (TMEM16A), was characterized using RT\u2010qPCR and immunohistochemistry. Tight junction (TJ) protein; zonula occludens (ZO\u20101) and basement membrane (BM) protein; and laminin were assessed by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Innate immune challenge prompted dysfunction in the exocrine SGs. Dysregulated gene and protein expression of molecules that drive saliva secretion was substantiated. Aberrant expression of TJ and BM proteins followed innate immune activation. Hyposalivation in the current model was independent of myeloperoxidase (MPO)\u2010positive, acute inflammatory cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this study, we developed a novel injury model of the SGs, featuring acute secretory dysfunction and immediate structural disruptions. Our results ruled out the injurious role of aggressively infiltrating inflammatory cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.12663","type":"journal-article","created":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T14:26:49Z","timestamp":1511274409000},"page":"211-219","source":"Crossref","is-referenced-by-count":4,"title":["Epithelial disruptions, but not immune cell invasion, induced secretory dysfunction following innate immune activation in a novel model of acute salivary gland injury"],"prefix":"10.1111","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9025-3885","authenticated-orcid":false,"given":"Abeer","family":"Shaalan","sequence":"first","affiliation":[{"name":"Mucosal and Salivary Biology Division Dental Institute King's College London Guy's Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3084-3415","authenticated-orcid":false,"given":"Guy","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Mucosal and Salivary Biology Division Dental Institute King's College London Guy's Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5684-841X","authenticated-orcid":false,"given":"Gordon","family":"Proctor","sequence":"additional","affiliation":[{"name":"Mucosal and Salivary Biology Division Dental Institute King's College London Guy's Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,12,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12116"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.12334"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-014-1848-2"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel067"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01546.2005"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.108.1.35"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.52.32956"},{"key":"e_1_2_7_9_1","first-page":"13","article-title":"Tight junctions and paracellular fluid and ion transport in salivary glands","volume":"16","author":"Zhang GH","year":"2013","journal-title":"Chin J Dent Res"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00011.2011"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2008.00700.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2012.01181.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1204697"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-06-435164"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830181125"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7007-7-77"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb923"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.4161\/cam.21831"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.4292\/wjgpt.v1.i1.15"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep313"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0959-9673.2006.00453.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)61435-3"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1415739112"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008760200"},{"key":"e_1_2_7_25_1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.4103\/2008-322X.170354","article-title":"Extracellular matrix components regulate cellular polarity and tissue structure in the developing and mature retina","volume":"10","author":"Varshney S","year":"2015","journal-title":"J Ophthalmic Vis Res"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.11.9.3045"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2016.1162348"}],"container-title":["Journal of Oral Pathology &amp; 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