{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T12:32:15Z","timestamp":1781008335800,"version":"3.54.1"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,7,28]],"date-time":"2014-07-28T00:00:00Z","timestamp":1406505600000},"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":"crossref","award":["81100766"],"award-info":[{"award-number":["81100766"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shanghai Municipal Commission of Health and Family Planning","award":["2014035"],"award-info":[{"award-number":["2014035"]}]},{"name":"Science and Technology Commission of Shanghai","award":["08DZ2271100"],"award-info":[{"award-number":["08DZ2271100"]}]},{"name":"Program for Innovative Research Team of Shanghai Municipal Education Commission"},{"name":"Shanghai Jiaotong University of Medicine Foundation","award":["YZ1024"],"award-info":[{"award-number":["YZ1024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2014,11]]},"abstract":"Objective<\/jats:title>The objective of this study was to investigate the potential role of T<\/jats:styled-content>oll\u2010like receptor 9\u2010dependent p38 MAPK<\/jats:styled-content> signaling pathway in the pathogenesis of primary S<\/jats:styled-content>j\u00f6gren's syndrome (pSS<\/jats:styled-content>) in NOD<\/jats:styled-content>\/L<\/jats:styled-content>tj mouse, aiming to identify an ideal target therapy model for human pSS<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>NOD<\/jats:styled-content>\/L<\/jats:styled-content>tj mice were chosen as a model of pSS<\/jats:styled-content>. The T<\/jats:styled-content>oll\u2010like receptor 9 and p\u2010p38 MAPK<\/jats:styled-content> double\u2010positive peripheral blood mononuclear cells (PBMC<\/jats:styled-content>s) of 4\u2010, 5\u2010, 8\u2010, 10\u2010, and 15\u2010week\u2010old NOD<\/jats:styled-content>\/L<\/jats:styled-content>tj mouse were analyzed by flow cytometry. The expressions of T<\/jats:styled-content>oll\u2010like receptor 9 and p\u2010p38 MAPK<\/jats:styled-content> in the submandibular gland (SMG<\/jats:styled-content>) were also examined by immunohistochemistry. The change of stimulated salivary flow rate was dynamically measured, and the histopathology of SMG<\/jats:styled-content> was evaluated by hematoxylin and eosin stain.<\/jats:p><\/jats:sec>Results<\/jats:title>The stimulated salivary flow rate in NOD<\/jats:styled-content>\/L<\/jats:styled-content>tj was reduced to 50\u201360% of the flow rate of control mice since the fifth week onwards. The T<\/jats:styled-content>oll\u2010like receptor 9 and p\u2010p38 MAPK<\/jats:styled-content> double\u2010positive PBMC<\/jats:styled-content>s in both groups increased gradually from 5\u00a0weeks, peaked at 8\u00a0weeks and then gradually decreased at 10\u00a0weeks, yet the percentage of T<\/jats:styled-content>oll\u2010like receptor 9 and p\u2010p38MAPK<\/jats:styled-content> double\u2010positive PBMC<\/jats:styled-content>s in 5\u2010, 8\u2010, and 10\u2010week\u2010old NOD<\/jats:styled-content>\/L<\/jats:styled-content>tj mouse was significantly increased compared with those in control subjects. After the 10th week onwards, there were no significant differences in the T<\/jats:styled-content>oll\u2010like receptor 9 and p\u2010p38 MAPK<\/jats:styled-content> double\u2010positive PBMC<\/jats:styled-content>s between NOD<\/jats:styled-content>\/L<\/jats:styled-content>tj mice and controls. Immunohistochemical staining showed that T<\/jats:styled-content>oll\u2010like receptor 9 was positive in the acinar epithelium cells and infiltrating lymphocytes in NOD<\/jats:styled-content>\/L<\/jats:styled-content>tj mice. p\u2010p38 MAPK<\/jats:styled-content> was detected in infiltrating lymphocytes and few ductal or acinar epithelium cells adjacent to infiltrating lymphocytes in NOD<\/jats:styled-content>\/L<\/jats:styled-content>tj mice.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>From the fifth week till the tenth week, T<\/jats:styled-content>oll\u2010like receptor 9 and p\u2010p38 MAPK<\/jats:styled-content> double\u2010positive PBMC<\/jats:styled-content>s were significantly increased in NOD<\/jats:styled-content>\/L<\/jats:styled-content>tj mice, accompanied with reduced stimulated salivary flow rate and T<\/jats:styled-content>oll\u2010like receptor 9 or p\u2010p38 MAPK<\/jats:styled-content> positive infiltrating lymphocytes observed in the SMG<\/jats:styled-content> of NOD<\/jats:styled-content>\/L<\/jats:styled-content>tj mouse. Our results indicated that activation of T<\/jats:styled-content>oll\u2010like receptor 9\u2010depended p38 MAPK<\/jats:styled-content> signal pathway in PBMC<\/jats:styled-content>s was an early event in pSS<\/jats:styled-content> which made NOD<\/jats:styled-content>\/L<\/jats:styled-content>tj as an ideal therapy model to test the treatment effects of p38 MAPK<\/jats:styled-content> or T<\/jats:styled-content>oll\u2010like receptor 9 inhibitors on pSS<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.12209","type":"journal-article","created":{"date-parts":[[2014,7,28]],"date-time":"2014-07-28T05:11:33Z","timestamp":1406524293000},"page":"785-791","source":"Crossref","is-referenced-by-count":22,"title":["Activation of TLR<\/scp>9\u2010dependent p38MAPK<\/scp> pathway in the pathogenesis of primary S<\/scp>j\u00f6gren's syndrome in NOD<\/scp>\/L<\/scp>tj mouse"],"prefix":"10.1111","volume":"43","author":[{"given":"Huan","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Oral Surgery Affiliated Shanghai 9th People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology 639 Zhi\u2010Zao\u2010Ju Road Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang\u2010Qi","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery Affiliated Shanghai 9th People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology 639 Zhi\u2010Zao\u2010Ju Road Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Song","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery Affiliated Shanghai 9th People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology 639 Zhi\u2010Zao\u2010Ju Road 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