{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:31:39Z","timestamp":1784824299685,"version":"3.55.0"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Grade C, Stage 3\u20134 Periodontitis (Perio4C) is a rapidly destructive disease caused by an unequilibrated immune response that starts after the primary contact of the periodontopathogens with the gingival tissue. However, it is still unclear how this imbalanced response initiates and what is the role of the connective tissue cells in the progression of this disease. Thus, this study aims to assess the local immune response of Perio4C patients through the exposure of primary gingival fibroblast cells (GFs) with <jats:italic>Aggregatibacter actinomycetemcomitans<\/jats:italic> protein extract (<jats:italic>Aa<\/jats:italic>PE) and the quantification of the inflammatory cytokines interleukin (IL)\u20104, IL\u201017, tumor necrosis factor (TNF)\u2010\u03b1, IL\u20101\u03b2, interferon (IFN)\u2010\u03b3, and IL\u201010 super\u2010family members (IL\u201010, IL\u201019, and IL\u201024) secreted by them.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gingival biopsies from nine periodontally health (PH) and eight Perio4C patients were harvested, and the primary culture of GFs was obtained. The cells were exposed to <jats:italic>Aa<\/jats:italic>PE (5 and 20\u00a0\u03bcg\/ml) and 12\u2010myristate 13\u2010phorbol acetate and ionomycin \u2013 calcium salt (PMA). The supernatant was collected after 1.5 and 3\u00a0h, and a cytokine panel was evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Clustering analysis indicated dissimilar and stimuli\u2010dependent cytokine production between Perio4C and PH subjects. Perio4C GFs presented lower production of IL\u20104, TNF\u2010\u03b1, IFN\u2010\u03b3, IL\u201017, IL\u201010, IL\u201024, and IL\u201019, while IL\u20101\u03b2 levels were similar to the PH group, leading to a disruption in the pro\u2010\/anti\u2010inflammatory cytokine ratio (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05). IL\u20101\u03b2 and IL\u201010 super\u2010family were the most discriminative representants for PH and Perio4C, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>GFs from individuals with Perio4C tended to hypo\u2010respond to stimulation with <jats:italic>Aa<\/jats:italic>PE, producing lower concentrations of some pro\u2010 and anti\u2010inflammatory molecules, trending to develop a pro\u2010inflammatory extracellular environment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.22-0356","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T12:02:33Z","timestamp":1665489753000},"page":"429-438","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Immune response characterization of primary gingival fibroblasts from Grade C periodontitis patients"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5125-2326","authenticated-orcid":false,"given":"Camila S.","family":"Stolf","sequence":"first","affiliation":[{"name":"Periodontics Division, Department of Prosthodontics and Periodontics, Piracicaba Dental School University of Campinas  Piracicaba SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina M.","family":"Sacramento","sequence":"additional","affiliation":[{"name":"Periodontics Division, Department of Prosthodontics and Periodontics, Piracicaba Dental School University of Campinas  Piracicaba SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina A. 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