{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T16:34:03Z","timestamp":1793637243482,"version":"4.5.1"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,5,9]],"date-time":"2012-05-09T00:00:00Z","timestamp":1336521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:p><jats:italic>Kim Y\u2010S, Shin S\u2010I, Kang K\u2010L, Herr Y, Bae W\u2010J, Kim E\u2010C. Nicotine and lipopolysaccharide stimulate the production of MMPs and prostaglandin E<jats:sub>2<\/jats:sub>by hypoxia\u2010inducible factor\u20101\u03b1 up\u2010regulation in human periodontal ligament cells. J Periodont Res 2012; 47: 719\u2013728. \u00a9 2012 John Wiley &amp; Sons A\/S<\/jats:italic><\/jats:p><jats:p><jats:bold>Background and Objective:\u2002<\/jats:bold>Although hypoxia\u2010inducible factor 1\u03b1 (HIF\u20101\u03b1) is up\u2010regulated in the periodontal pockets of periodontitis patients, the expression and precise molecular mechanisms of HIF\u20101\u03b1 remain unknown in human periodontal ligament cells (PDLCs). The aim of this study was to explore the effects, as well as the signaling pathway, of nicotine and lipopolysaccharide (LPS) on the expression of HIF\u20101\u03b1 and on the production of its target genes, including cyclooxygenase\u20102 (COX\u20102)\u2010derived prostaglandin E<jats:sub>2<\/jats:sub>(PGE<jats:sub>2<\/jats:sub>), MMP\u20102 and MMP\u20109 in PDLCs.<\/jats:p><jats:p><jats:bold>Material and Methods:\u2002<\/jats:bold>The expression of COX\u20102 and HIF\u20101\u03b1 proteins was evaluated using western blotting. The production of PGE<jats:sub>2<\/jats:sub>and MMPs was evaluated using enzyme immunoassays and zymography, respectively.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold>LPS and nicotine synergistically induced the production of PGE<jats:sub>2<\/jats:sub>, MMP\u20102 and MMP\u20109, and increased the expression of MMP\u20102, MMP\u20109, COX\u20102 and HIF\u20101\u03b1 proteins. Inhibition of HIF\u20101\u03b1 activity by chetomin or knockdown of<jats:italic>HIF1\u03b1<\/jats:italic>gene expression by small interfering RNA markedly attenuated the production of LPS\u2010 and nicotine\u2010stimulated PGE<jats:sub>2<\/jats:sub>and MMPs, as well as the expression of COX\u20102 and HIF\u20101\u03b1. Furthermore, pretreatment with inhibitors of COX\u20102, p38, extracellular signal\u2010regulated kinase, Jun N\u2010terminal kinase, protein kinase C, phosphatidylinositol 3\u2010kinase and nuclear factor\u2010kappaB decreased the expression of nicotine\u2010 and LPS\u2010induced HIF\u20101\u03b1 and COX\u20102, as well as the activity of PGE<jats:sub>2<\/jats:sub>and MMPs.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold>These data demonstrate novel mechanisms by which nicotine and LPS promote periodontal tissue destruction, and provide further evidence that HIF\u20101\u03b1 is a potential target in periodontal disease associated with smoking and dental plaque.<\/jats:p>","DOI":"10.1111\/j.1600-0765.2012.01487.x","type":"journal-article","created":{"date-parts":[[2012,5,10]],"date-time":"2012-05-10T02:30:07Z","timestamp":1336617007000},"page":"719-728","source":"Crossref","is-referenced-by-count":43,"title":["Nicotine and lipopolysaccharide stimulate the production of MMPs and prostaglandin E<sub>2<\/sub>by hypoxia\u2010inducible factor\u20101\u03b1 up\u2010regulation in human periodontal ligament cells"],"prefix":"10.1111","volume":"47","author":[{"given":"Y\u2010S.","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u2010I.","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u2010L.","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u2010H.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Herr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W\u2010J.","family":"Bae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E\u2010C.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,5,9]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/1043-4666(90)90026-P"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/00220345950740040501"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2007.060217"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-5712(96)00084-X"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1989.60.9.485"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/10454411930040020401"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/00220345940730080201"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.2005.00245.x"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1996.tb01814.x"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/07853890600800103"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.2007.00212.x"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1989.60.4.176"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2006.00937.x"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7270.2006.00240.x"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2009.090098"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2008.09.017"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2005.08.017"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7270.2007.00271.x"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2009.01215.x"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(98)80016-6"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.9.4604"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0329fje"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20051839"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-2898"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2010.100100"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3500307"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.08.142"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2011.01432.x"},{"key":"e_1_2_6_30_2","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1093\/oso\/9780195064414.003.0002","volume-title":"Nicotine Addiction. 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