{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T21:29:40Z","timestamp":1762896580888},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,11,29]],"date-time":"2014-11-29T00:00:00Z","timestamp":1417219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Medical Research Council"},{"name":"St Barts & the Royal London Charitable Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>In periodontitis the host response to bacterial challenge includes activity of the multifunctional molecules adrenomedullin (<jats:styled-content style=\"fixed-case\">AM<\/jats:styled-content>) and nitric oxide (<jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>). The aim of this study was to investigate the role of periodontal bacteria in regulating the production of these molecules from cultured cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>Regulation of AM and NO production from oral keratinocytes when challenged with culture supernatants from <jats:italic>Aggregatibacter actinomycetemcomitans<\/jats:italic>,<jats:italic> Campylobacter rectus<\/jats:italic>,<jats:italic> Fusobacterium nucleatum<\/jats:italic>,<jats:italic> Porphyromonas gingivalis<\/jats:italic>,<jats:italic> Prevotella intermedia<\/jats:italic>,<jats:italic> Veillonella atypica<\/jats:italic>,<jats:italic> Streptococcus salivarius<\/jats:italic> and <jats:italic>Candida albicans<\/jats:italic> was examined. AM and NO were measured in cell culture supernatants using an enzyme\u2010linked immunosorbent assay and the nitrate\/nitrite (NO metabolites) Griess assay respectively. Cellular production of AM and inducible NO synthase was also analysed in target cells by immunofluorescence and Western blot analysis. The inter\u2010relationship of AM and NO production were further investigated with macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>A.\u00a0actinomycetemcomitans<\/jats:italic> and <jats:italic>C.\u00a0rectus<\/jats:italic> induced maximal levels of both AM and NO after 6 and 48\u00a0h respectively from oral keratinocytes. AM production in macrophages was upregulated in response to the NO donor <jats:italic>S<\/jats:italic>\u2010nitrosoglutathione and partially blocked by the inducible NO synthase inhibitor, <jats:italic>N<\/jats:italic><jats:sup>\u03c9<\/jats:sup>\u2010Nitro\u2010<jats:sc>l<\/jats:sc>\u2010arginine methyl ester hydrochloride. Likewise, NO production was increased upon exposure to AM, while the AM receptor antagonist AM 22\u201052 reduced the release of NO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Pathogens associated with aggressive periodontitis, <jats:italic>A.\u00a0actinomycetemcomitans<\/jats:italic> and <jats:italic>C.\u00a0rectus<\/jats:italic>, were more effective than those associated with chronic periodontitis, <jats:italic>P.\u00a0gingivalis<\/jats:italic> and <jats:italic>Prev.\u00a0intermedia<\/jats:italic>, and commensals, <jats:italic>S.\u00a0salivarius<\/jats:italic> and <jats:italic>V.\u00a0atypica<\/jats:italic>, as regards the upregulation of <jats:styled-content style=\"fixed-case\">AM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> production from oral keratinocytes. Interaction between these molecules was also demonstrated with macrophages. Understanding the coordinated regulation of <jats:styled-content style=\"fixed-case\">AM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> production in response to periodontal bacteria may identify ways to promote their protective effects and minimize destructive potential.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12246","type":"journal-article","created":{"date-parts":[[2014,11,29]],"date-time":"2014-11-29T08:20:32Z","timestamp":1417249232000},"page":"650-657","source":"Crossref","is-referenced-by-count":17,"title":["Regulation of adrenomedullin and nitric oxide production by periodontal bacteria"],"prefix":"10.1111","volume":"50","author":[{"given":"Q. A.","family":"Hussain","sequence":"first","affiliation":[{"name":"Institute of Dentistry, Barts and The London School of Medicine &amp; Dentistry Queen Mary University of London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I. J.","family":"McKay","sequence":"additional","affiliation":[{"name":"Institute of Dentistry, Barts and The London School of Medicine &amp; Dentistry Queen Mary University of London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Gonzales\u2010Marin","sequence":"additional","affiliation":[{"name":"Institute of Dentistry, Barts and The London School of Medicine &amp; Dentistry Queen Mary University of London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. P.","family":"Allaker","sequence":"additional","affiliation":[{"name":"Institute of Dentistry, Barts and The London School of Medicine &amp; Dentistry Queen Mary University of London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,11,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-051x.2000.027009648.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2337"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-0115(03)00033-8"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0765.2000.035006369.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.10058"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/21.Supplement_2.S162"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1601-0825.2001.70102.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.140.11.5402"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.0452"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.1999.tb01250.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2005.08.006"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2001.72.5.590"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(99)00358-6"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0722.2004.00153.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend.14.6.0473"},{"key":"e_1_2_6_17_1","first-page":"77","article-title":"Inducible nitric oxide synthase is present within human atherosclerotic lesions and promotes the formation and activity of peroxynitrite","volume":"75","author":"Buttery LD","year":"1996","journal-title":"Lab Invest"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00822.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096203"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2004.00757.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1075-9964(03)00003-9"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.6.2736-2742.1998"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2005.07.014"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(01)00470-3"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.6.H2620"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-0749"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.10.2560"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703502"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-302X.2003.00049.x"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2013.130172"},{"key":"e_1_2_6_31_1","first-page":"373","volume-title":"Topley and Wilson's Microbiology and Microbial Infections","author":"Allaker RP","year":"1998"}],"container-title":["Journal of Periodontal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjre.12246","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjre.12246","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jre.12246","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T04:06:47Z","timestamp":1696219607000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jre.12246"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,29]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1111\/jre.12246"],"URL":"https:\/\/doi.org\/10.1111\/jre.12246","archive":["Portico"],"relation":{},"ISSN":["0022-3484","1600-0765"],"issn-type":[{"value":"0022-3484","type":"print"},{"value":"1600-0765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,29]]}}}