{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:07:01Z","timestamp":1791234421636,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T00:00:00Z","timestamp":1687132800000},"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","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013099","name":"Scientific Research Fund of Liaoning Provincial Education Department","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013099","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the critical roles of PU.1\/cathepsin S activation in regulating inflammatory responses of macrophages during periodontitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Background<\/jats:title><jats:p>Cathepsin S (CatS) is a cysteine protease and exerts important roles in the immune response. Elevated CatS has been found in the gingival tissues of periodontitis patients and is involved in alveolar bone destruction. However, the underlying mechanism of CatS\u2010driven IL\u20106 production in periodontitis remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Western blot was applied to measure mature cathepsin S(mCatS) and IL\u20106 expression in gingival tissues from periodontitis patients and RAW264.7 cells exposed to lipopolysaccharide from <jats:italic>Porphyromonas gingivalis<\/jats:italic> (<jats:italic>P.g.<\/jats:italic> LPS). Immunofluorescence was applied to confirm the localization of PU.1, and CatS in the gingival tissues of periodontitis patients. ELISA was performed to determine IL\u20106 production by the <jats:italic>P.g.<\/jats:italic> LPS\u2010exposed RAW264.7 cells. Knockdown by shRNA was used to determine the effects of PU.1 on p38\/ nuclear factor (NF)\u2010\u03baB activation, mCatS expression and IL\u20106 production in RAW264.7 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expressions mCatS and IL\u20106 were significantly upregulated in gingival macrophages. In cultured RAW264.7 cells, increased mCatS and IL\u20106 protein paralleled the activation of p38 and NF\u2010\u03baB after exposure to <jats:italic>P.g.<\/jats:italic> LPS. CatS knockdown by shRNA significantly decreased <jats:italic>P.g.<\/jats:italic> LPS\u2010induced IL\u20106 expression and p38\/NF\u2010\u03baB activation. PU.1 was significantly increased in <jats:italic>P.g.<\/jats:italic> LPS\u2010exposed RAW264.7 cells, and PU.1 knockdown dramatically abolished the <jats:italic>P.g.<\/jats:italic> LPS\u2010induced upregulation of mCatS and IL\u20106 and the activation of p38 and NF\u2010\u03baB. Furthermore, PU.1 and CatS colocalized in macrophages within the gingival tissues of periodontitis patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PU.1\u2010dependent CatS drives IL\u20106 production in macrophages by activating p38 and NF\u2010\u03baB in periodontitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.13153","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T09:05:11Z","timestamp":1687165511000},"page":"939-947","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Critical roles of <scp>PU<\/scp>.1\/cathepsin S activation in regulating inflammatory responses of macrophages in periodontitis"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3108-0800","authenticated-orcid":false,"given":"Kaige","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Oral Implantology, Liaoning 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