{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T20:02:31Z","timestamp":1762113751273,"version":"3.37.3"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T00:00:00Z","timestamp":1542153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["30973331","81500878","81570995","81801001"],"award-info":[{"award-number":["30973331","81500878","81570995","81801001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Sialadenitis is a nonneoplastic disease that causes salivary dysfunction. Autophagy may be involved in helping protect salivary function when the salivary gland is impaired; this process is primarily activated by sensors of innate immunity, such as Toll\u2010like receptors and nucleotide\u2010binding oligomerization domain (NOD)\u2010like receptors. The role of these pattern recognition receptors (PRRs) in the regulation of salivary gland tissue defense and homeostasis has been underappreciated. This study hypothesized that NOD2 and TLR4 have a synergistic effect on the activation of autophagy in human submandibular gland (HSG) inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Submandibular gland inflammation was modeled by treating HSG cell lines in\u00a0vitro with muramyl dipeptide (MDP) and lipopolysaccharide (LPS) for 24\u00a0hours. The mRNA and protein expression of NOD2, TLR4 and autophagy\u2010related proteins (ATG5, LC3, Beclin1) were evaluated by real\u2010time PCR and Western blot. Immunohistochemistry and double immunofluorescence were used to analyze the presence, distribution and colocalization of the aforementioned indicators in HSG tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>The mRNA and protein expression of autophagy\u2010related proteins were significantly increased in HSG cells costimulated with LPS and MDP for 24\u00a0hours. NOD2, TLR4 and the autophagy\u2010related proteins were also highly expressed in residual acini and dilated ducts of chronic submandibular sialadenitis tissues. In addition, PRRs and autophagy markers were obviously colocalized in chronic submandibular sialadenitis tissues and HSG cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>TLR4 and NOD2 have unique expression sites in salivary glands, and they may synergistically activate autophagy in salivary glands under conditions of inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.12793","type":"journal-article","created":{"date-parts":[[2018,10,27]],"date-time":"2018-10-27T06:28:41Z","timestamp":1540621721000},"page":"87-95","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The synergistic effect of NOD2 and TLR4 on the activation of autophagy in human submandibular gland inflammation"],"prefix":"10.1111","volume":"48","author":[{"given":"Jiajie","family":"Li","sequence":"first","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) and Key Laboratory of Oral Biomedicine Ministry of Education School and Hospital of Stomatology Wuhan University Wuhan China"},{"name":"Department of Oral Radiology School and Hospital of Stomatology Wuhan University Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) and Key Laboratory of Oral Biomedicine Ministry of Education School and Hospital of Stomatology Wuhan University Wuhan China"},{"name":"Department of Oral Radiology School and Hospital of Stomatology Wuhan University Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7434-8761","authenticated-orcid":false,"given":"Yong","family":"Cheng","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) and Key Laboratory 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