{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T12:51:58Z","timestamp":1777812718449,"version":"3.51.4"},"reference-count":30,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2012,7,24]],"date-time":"2012-07-24T00:00:00Z","timestamp":1343088000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:p>\n                    Levels of prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ) and its processing enzyme, prostaglandin-endoperoxide-synthase-2\/ cyclooxygenase-2 (PTGS2\/COX-2), are elevated in actively progressing periodontal lesions, but suppressed in chronic disease. COX-2 expression is regulated through inflammatory signaling that converges on the mitogen-activated protein kinase (MAPK) pathway. Emerging evidence suggests a role for the inflammatory adaptor protein, ASC\/Pycard, in MAPK activation. We postulated that ASC may represent a mediator of the MAPK-mediated regulatory network of PGE\n                    <jats:sub>2<\/jats:sub>\n                    production. Using RNAi-mediated gene slicing, we demonstrated that ASC regulates COX-2 expression and PGE\n                    <jats:sub>2<\/jats:sub>\n                    production in THP1 monocytic cells following infection with Porphyromonas gingivalis (Pg). Production of PGE\n                    <jats:sub>2<\/jats:sub>\n                    did not require the inflammasome adaptor function of ASC, but was dependent on MAPK activation. Furthermore, the MAP kinase kinase kinase CARD domain-containing protein RIPK2 was induced by Pg in an ASC-dependent manner. Reduced ASC and RIPK2 levels were revealed by orthogonal comparison of the expression of the RIPK family in ASC-deficient THP1 cells with that in chronic periodontitis patients. We show that pharmacological inhibition of RIPK2 represses PGE\n                    <jats:sub>2<\/jats:sub>\n                    secretion, and RNAi-mediated silencing of RIPK2 leads to diminished MAPK activation and PGE\n                    <jats:sub>2<\/jats:sub>\n                    secretion. These findings identify a novel ASC-RIPK2 axis in the generation of PGE\n                    <jats:sub>2<\/jats:sub>\n                    that is repressed in patients diagnosed with chronic adult periodontitis.\n                  <\/jats:p>","DOI":"10.1177\/0022034512454541","type":"journal-article","created":{"date-parts":[[2012,7,25]],"date-time":"2012-07-25T02:29:32Z","timestamp":1343183372000},"page":"877-882","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["ASC-dependent RIP2 Kinase Regulates Reduced PGE\n                    <sub>2<\/sub>\n                    Production in Chronic Periodontitis"],"prefix":"10.1177","volume":"91","author":[{"given":"D.J.","family":"Taxman","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine; University of North Carolina, Chapel Hill, NC, USA"},{"name":"Lineberger Comprehensive Cancer Center; University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine; University of North Carolina, Chapel Hill, NC, USA"},{"name":"Lineberger Comprehensive Cancer Center; University of North Carolina, Chapel Hill, NC, USA"},{"name":"North Carolina Oral Health Institute, School of Dentistry; University of North Carolina, Chapel Hill, NC, USA"},{"name":"Oral and Maxillofacial Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Zhang","sequence":"additional","affiliation":[{"name":"North Carolina Oral Health Institute, School of Dentistry; University of North Carolina, Chapel Hill, NC, USA"},{"name":"Department of Periodontology, School of Dentistry; University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Holley-Guthrie","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine; University of North Carolina, Chapel Hill, NC, USA"},{"name":"Lineberger Comprehensive Cancer Center; University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Offenbacher","sequence":"additional","affiliation":[{"name":"North Carolina Oral Health Institute, School of Dentistry; University of North Carolina, Chapel Hill, NC, USA"},{"name":"Department of Periodontology, School of Dentistry; University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.P.-Y.","family":"Ting","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine; University of North Carolina, Chapel Hill, NC, USA"},{"name":"Lineberger Comprehensive Cancer Center; University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2012,7,24]]},"reference":[{"key":"bibr1-0022034512454541","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20070797"},{"key":"bibr2-0022034512454541","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.1997.tb00565.x"},{"key":"bibr3-0022034512454541","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2009.05.005"},{"key":"bibr4-0022034512454541","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2009.03972.x"},{"key":"bibr5-0022034512454541","doi-asserted-by":"publisher","DOI":"10.1016\/S0083-6729(04)67008-7"},{"key":"bibr6-0022034512454541","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01041.x"},{"key":"bibr7-0022034512454541","first-page":"1","volume-title":"International Workshop for a Classification of Periodontal Diseases and Conditions","volume":"4","author":"Caton 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