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Melatonin Receptor Agonists as the "Perioceutics" Agents for Periodontal Disease through Modulation of Porphyromonas gingivalis Virulence and Inflammatory Response
"Perioceutics" including antimicrobial therapy and host modulatory therapy has emerged as a vital adjunctive treatment of periodontal disease. Melatonin level was significantly reduced in patients with periodontal diseases suggesting melatonin could be applied as a potential "perioceu...
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| Published in: | PloS one 2016-11, Vol.11 (11), p.e0166442-e0166442 |
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| container_end_page | e0166442 |
| container_issue | 11 |
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| creator | Zhou, Wei Zhang, Xuan Zhu, Cai-Lian He, Zhi-Yan Liang, Jing-Ping Song, Zhong-Chen |
| description | "Perioceutics" including antimicrobial therapy and host modulatory therapy has emerged as a vital adjunctive treatment of periodontal disease. Melatonin level was significantly reduced in patients with periodontal diseases suggesting melatonin could be applied as a potential "perioceutics" treatment of periodontal diseases. This study aims to investigate the effects of melatonin receptor agonists (melatonin and ramelteon) on Porphyromonas gingivalis virulence and Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS)-induced inflammation.
Effects of melatonin receptor agonists on Porphyromonas gingivalis planktonic cultures were determined by microplate dilution assays. Formation, reduction, and viability of Porphyromonas gingivalis biofilms were detected by crystal violet staining and MTT assays, respectively. Meanwhile, biofilms formation was also observed by confocal laser scanning microscopy (CLSM). The effects on gingipains and hemolytic activities of Porphyromonas gingivalis were evaluated using chromogenic peptides and sheep erythrocytes. The mRNA expression of virulence and iron/heme utilization was assessed using RT-PCR. In addition, cell viability of melatonin receptor agonists on human gingival fibroblasts (HGFs) was evaluated by MTT assays. After pretreatment of melatonin receptor agonists, HGFs were stimulated with Pg-LPS and then release of cytokines (IL-6 and lL-8) was measured by enzyme-linked immunosorbent assay (ELISA).
Melatonin and ramelteon did exhibit antimicrobial effects against planktonic culture. Importantly, they inhibited biofilm formation, reduced the established biofilms, and decreased biofilm viability of Porphyromonas gingivalis. Furthermore, they at sub-minimum inhibitory concentration (sub-MIC) concentrations markedly inhibited the proteinase activities of gingipains and hemolysis in a dose-dependent manner. They at sub-MIC concentrations significantly inhibited the mRNA expression of virulence factors (kgp, rgpA, rgpB, hagA, and ragA), while increasing the mRNA expression of ferritin (ftn) or hemolysin (hem). They did not show obvious cytotoxicity toward HGFs. They inhibited Pg-LPS-induced IL-6 and IL-8 secretion, which was reversed by luzindole, the melatonin receptor antagonist.
Melatonin receptor agonists can inhibit planktonic and biofilm growth of Porphyromonas gingivalis by affecting the virulent properties, as well as Pg-LPS-induced inflammatory response. Our study provides new evidence that melatonin recepto |
| doi_str_mv | 10.1371/journal.pone.0166442 |
| format | article |
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Effects of melatonin receptor agonists on Porphyromonas gingivalis planktonic cultures were determined by microplate dilution assays. Formation, reduction, and viability of Porphyromonas gingivalis biofilms were detected by crystal violet staining and MTT assays, respectively. Meanwhile, biofilms formation was also observed by confocal laser scanning microscopy (CLSM). The effects on gingipains and hemolytic activities of Porphyromonas gingivalis were evaluated using chromogenic peptides and sheep erythrocytes. The mRNA expression of virulence and iron/heme utilization was assessed using RT-PCR. In addition, cell viability of melatonin receptor agonists on human gingival fibroblasts (HGFs) was evaluated by MTT assays. After pretreatment of melatonin receptor agonists, HGFs were stimulated with Pg-LPS and then release of cytokines (IL-6 and lL-8) was measured by enzyme-linked immunosorbent assay (ELISA).
Melatonin and ramelteon did exhibit antimicrobial effects against planktonic culture. Importantly, they inhibited biofilm formation, reduced the established biofilms, and decreased biofilm viability of Porphyromonas gingivalis. Furthermore, they at sub-minimum inhibitory concentration (sub-MIC) concentrations markedly inhibited the proteinase activities of gingipains and hemolysis in a dose-dependent manner. They at sub-MIC concentrations significantly inhibited the mRNA expression of virulence factors (kgp, rgpA, rgpB, hagA, and ragA), while increasing the mRNA expression of ferritin (ftn) or hemolysin (hem). They did not show obvious cytotoxicity toward HGFs. They inhibited Pg-LPS-induced IL-6 and IL-8 secretion, which was reversed by luzindole, the melatonin receptor antagonist.
Melatonin receptor agonists can inhibit planktonic and biofilm growth of Porphyromonas gingivalis by affecting the virulent properties, as well as Pg-LPS-induced inflammatory response. Our study provides new evidence that melatonin receptor agonists might be useful as novel "perioceutics" agents to prevent and treat Porphyromonas gingivalis-associated periodontal diseases.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0166442</identifier><identifier>PMID: 27832188</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Anti-Bacterial Agents - pharmacology ; Anti-Inflammatory Agents - pharmacology ; Antiinfectives and antibacterials ; Antimicrobial agents ; Assaying ; Bacteria ; Biofilms ; Biofilms - drug effects ; Biology and Life Sciences ; Cell culture ; Cells, Cultured ; Confocal microscopy ; Cytokines ; Cytotoxicity ; Dilution ; Disease ; Diseases ; Enzyme-linked immunosorbent assay ; Enzymes ; Erythrocytes ; Ferritin ; Fibroblasts ; Fibroblasts - drug effects ; Fibroblasts - immunology ; Fibroblasts - microbiology ; Gene expression ; Gene Expression Regulation, Bacterial - drug effects ; Gum disease ; Heme ; Hemoglobin ; Hemolysis - drug effects ; Hospitals ; Humans ; Indenes - pharmacology ; Inflammation ; Inflammatory response ; Interleukin 6 ; Interleukin 8 ; Interleukin-6 - immunology ; Interleukin-8 - immunology ; Iron ; Laboratories ; Lipopolysaccharides ; Medical research ; Medical treatment ; Medicine ; Medicine and Health Sciences ; Melatonin ; Melatonin - pharmacology ; Microscopy ; Minimum inhibitory concentration ; Mitogens ; Pathogens ; Peptides ; Periodontal disease ; Periodontal diseases ; Periodontal Diseases - drug therapy ; Periodontal Diseases - immunology ; Polymerase chain reaction ; Porphyromonas gingivalis ; Porphyromonas gingivalis - drug effects ; Porphyromonas gingivalis - immunology ; Porphyromonas gingivalis - pathogenicity ; Porphyromonas gingivalis - physiology ; Proteinase ; Ragas ; Receptors, Melatonin - agonists ; RNA ; Sheep ; Studies ; Therapy ; Toxicity ; Virulence ; Virulence (Microbiology) ; Virulence factors</subject><ispartof>PloS one, 2016-11, Vol.11 (11), p.e0166442-e0166442</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Zhou et al 2016 Zhou et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c791t-ac2479bf70b192a60ac6be5ced72d8d8f62fdceec449f660b1894a59803971093</citedby><cites>FETCH-LOGICAL-c791t-ac2479bf70b192a60ac6be5ced72d8d8f62fdceec449f660b1894a59803971093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1838211897/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1838211897?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,25783,27957,27958,37047,37048,44625,53827,53829,75483</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27832188$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ho, Yuan-Soon</contributor><creatorcontrib>Zhou, Wei</creatorcontrib><creatorcontrib>Zhang, Xuan</creatorcontrib><creatorcontrib>Zhu, Cai-Lian</creatorcontrib><creatorcontrib>He, Zhi-Yan</creatorcontrib><creatorcontrib>Liang, Jing-Ping</creatorcontrib><creatorcontrib>Song, Zhong-Chen</creatorcontrib><title>Melatonin Receptor Agonists as the "Perioceutics" Agents for Periodontal Disease through Modulation of Porphyromonas gingivalis Virulence and Inflammatory Response</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>"Perioceutics" including antimicrobial therapy and host modulatory therapy has emerged as a vital adjunctive treatment of periodontal disease. Melatonin level was significantly reduced in patients with periodontal diseases suggesting melatonin could be applied as a potential "perioceutics" treatment of periodontal diseases. This study aims to investigate the effects of melatonin receptor agonists (melatonin and ramelteon) on Porphyromonas gingivalis virulence and Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS)-induced inflammation.
Effects of melatonin receptor agonists on Porphyromonas gingivalis planktonic cultures were determined by microplate dilution assays. Formation, reduction, and viability of Porphyromonas gingivalis biofilms were detected by crystal violet staining and MTT assays, respectively. Meanwhile, biofilms formation was also observed by confocal laser scanning microscopy (CLSM). The effects on gingipains and hemolytic activities of Porphyromonas gingivalis were evaluated using chromogenic peptides and sheep erythrocytes. The mRNA expression of virulence and iron/heme utilization was assessed using RT-PCR. In addition, cell viability of melatonin receptor agonists on human gingival fibroblasts (HGFs) was evaluated by MTT assays. After pretreatment of melatonin receptor agonists, HGFs were stimulated with Pg-LPS and then release of cytokines (IL-6 and lL-8) was measured by enzyme-linked immunosorbent assay (ELISA).
Melatonin and ramelteon did exhibit antimicrobial effects against planktonic culture. Importantly, they inhibited biofilm formation, reduced the established biofilms, and decreased biofilm viability of Porphyromonas gingivalis. Furthermore, they at sub-minimum inhibitory concentration (sub-MIC) concentrations markedly inhibited the proteinase activities of gingipains and hemolysis in a dose-dependent manner. They at sub-MIC concentrations significantly inhibited the mRNA expression of virulence factors (kgp, rgpA, rgpB, hagA, and ragA), while increasing the mRNA expression of ferritin (ftn) or hemolysin (hem). They did not show obvious cytotoxicity toward HGFs. They inhibited Pg-LPS-induced IL-6 and IL-8 secretion, which was reversed by luzindole, the melatonin receptor antagonist.
Melatonin receptor agonists can inhibit planktonic and biofilm growth of Porphyromonas gingivalis by affecting the virulent properties, as well as Pg-LPS-induced inflammatory response. Our study provides new evidence that melatonin receptor agonists might be useful as novel "perioceutics" agents to prevent and treat Porphyromonas gingivalis-associated periodontal diseases.</description><subject>Animals</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Antiinfectives and antibacterials</subject><subject>Antimicrobial agents</subject><subject>Assaying</subject><subject>Bacteria</subject><subject>Biofilms</subject><subject>Biofilms - drug effects</subject><subject>Biology and Life Sciences</subject><subject>Cell culture</subject><subject>Cells, Cultured</subject><subject>Confocal microscopy</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Dilution</subject><subject>Disease</subject><subject>Diseases</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Enzymes</subject><subject>Erythrocytes</subject><subject>Ferritin</subject><subject>Fibroblasts</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - immunology</subject><subject>Fibroblasts - microbiology</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Bacterial - drug effects</subject><subject>Gum disease</subject><subject>Heme</subject><subject>Hemoglobin</subject><subject>Hemolysis - drug effects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Indenes - pharmacology</subject><subject>Inflammation</subject><subject>Inflammatory response</subject><subject>Interleukin 6</subject><subject>Interleukin 8</subject><subject>Interleukin-6 - immunology</subject><subject>Interleukin-8 - immunology</subject><subject>Iron</subject><subject>Laboratories</subject><subject>Lipopolysaccharides</subject><subject>Medical research</subject><subject>Medical treatment</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Melatonin</subject><subject>Melatonin - pharmacology</subject><subject>Microscopy</subject><subject>Minimum inhibitory concentration</subject><subject>Mitogens</subject><subject>Pathogens</subject><subject>Peptides</subject><subject>Periodontal disease</subject><subject>Periodontal diseases</subject><subject>Periodontal Diseases - drug therapy</subject><subject>Periodontal Diseases - immunology</subject><subject>Polymerase chain reaction</subject><subject>Porphyromonas gingivalis</subject><subject>Porphyromonas gingivalis - drug effects</subject><subject>Porphyromonas gingivalis - immunology</subject><subject>Porphyromonas gingivalis - pathogenicity</subject><subject>Porphyromonas gingivalis - physiology</subject><subject>Proteinase</subject><subject>Ragas</subject><subject>Receptors, Melatonin - agonists</subject><subject>RNA</subject><subject>Sheep</subject><subject>Studies</subject><subject>Therapy</subject><subject>Toxicity</subject><subject>Virulence</subject><subject>Virulence (Microbiology)</subject><subject>Virulence factors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tu1DAQhiMEoqXwBgiiIiG42MWnxM4N0qqcVmrVqkBvLa89ybpy7K2dVPR5eFG87bbqol5Uvojj-f7f47GnKF5jNMWU40_nYYxeuekqeJgiXNeMkSfFLm4omdQE0af35jvFi5TOEaqoqOvnxQ7hghIsxG7x9wicGoK3vjwFDashxHLW5f80pFKlclhCuX8C0QYN42B12s9h8DnYZvI6YIIflCu_2AQqQVbEMHbL8iiYMVvb4MvQlichrpZXMfTBZ9fO-s5eKmdTeWbj6MBrKJU35dy3TvV9zihe5YRSPlyCl8WzVrkErzbfveL3t6-_Dn5MDo-_zw9mhxPNGzxMlCaMN4uWowVuiKqR0vUCKg2GEyOMaGvSGg2gGWvaus6UaJiqGoFowzFq6F7x9sZ35UKSm_omiQUVBGeYZ2J-Q5igzuUq2l7FKxmUldcLIXZSxVwlBxIpMIgYVjVowThtBcemMRpzxCu9qGn2-rzZbVz0kBPzQ1Ruy3Q74u1SduFSVhgxKnA2-LAxiOFihDTI3iYNzikPYVznzWpGMOfkEShtMGZE1Bl99x_6cCE2VKfyWa1vQ05Rr03ljHEsKorQetvpA1QeBnqr87ttbV7fEnzcEmRmgD9Dp8aU5Pzn6ePZ47Nt9v09dgnKDcsU3Lh-nWkbZDegjiGlCO3dfWAk1213Ww25bju5absse3P_Lu9Et31G_wGx7Spg</recordid><startdate>20161110</startdate><enddate>20161110</enddate><creator>Zhou, Wei</creator><creator>Zhang, Xuan</creator><creator>Zhu, Cai-Lian</creator><creator>He, Zhi-Yan</creator><creator>Liang, Jing-Ping</creator><creator>Song, Zhong-Chen</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20161110</creationdate><title>Melatonin Receptor Agonists as the "Perioceutics" Agents for Periodontal Disease through Modulation of Porphyromonas gingivalis Virulence and Inflammatory Response</title><author>Zhou, Wei ; Zhang, Xuan ; Zhu, Cai-Lian ; He, Zhi-Yan ; Liang, Jing-Ping ; Song, Zhong-Chen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c791t-ac2479bf70b192a60ac6be5ced72d8d8f62fdceec449f660b1894a59803971093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Anti-Bacterial Agents - 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pharmacology</topic><topic>Inflammation</topic><topic>Inflammatory response</topic><topic>Interleukin 6</topic><topic>Interleukin 8</topic><topic>Interleukin-6 - immunology</topic><topic>Interleukin-8 - immunology</topic><topic>Iron</topic><topic>Laboratories</topic><topic>Lipopolysaccharides</topic><topic>Medical research</topic><topic>Medical treatment</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Melatonin</topic><topic>Melatonin - pharmacology</topic><topic>Microscopy</topic><topic>Minimum inhibitory concentration</topic><topic>Mitogens</topic><topic>Pathogens</topic><topic>Peptides</topic><topic>Periodontal disease</topic><topic>Periodontal diseases</topic><topic>Periodontal Diseases - drug therapy</topic><topic>Periodontal Diseases - immunology</topic><topic>Polymerase chain reaction</topic><topic>Porphyromonas gingivalis</topic><topic>Porphyromonas gingivalis - drug effects</topic><topic>Porphyromonas gingivalis - immunology</topic><topic>Porphyromonas gingivalis - pathogenicity</topic><topic>Porphyromonas gingivalis - physiology</topic><topic>Proteinase</topic><topic>Ragas</topic><topic>Receptors, Melatonin - agonists</topic><topic>RNA</topic><topic>Sheep</topic><topic>Studies</topic><topic>Therapy</topic><topic>Toxicity</topic><topic>Virulence</topic><topic>Virulence (Microbiology)</topic><topic>Virulence factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Wei</creatorcontrib><creatorcontrib>Zhang, Xuan</creatorcontrib><creatorcontrib>Zhu, Cai-Lian</creatorcontrib><creatorcontrib>He, Zhi-Yan</creatorcontrib><creatorcontrib>Liang, Jing-Ping</creatorcontrib><creatorcontrib>Song, Zhong-Chen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints Resource Center</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Wei</au><au>Zhang, Xuan</au><au>Zhu, Cai-Lian</au><au>He, Zhi-Yan</au><au>Liang, Jing-Ping</au><au>Song, Zhong-Chen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Melatonin Receptor Agonists as the "Perioceutics" Agents for Periodontal Disease through Modulation of Porphyromonas gingivalis Virulence and Inflammatory Response</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-11-10</date><risdate>2016</risdate><volume>11</volume><issue>11</issue><spage>e0166442</spage><epage>e0166442</epage><pages>e0166442-e0166442</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>Conceptualization: WZ JPL ZCS.Formal analysis: WZ XZ.Funding acquisition: WZ ZCS.Investigation: WZ XZ JPL ZCS.Methodology: WZ XZ CLZ ZYH.Project administration: JPL ZCS.Resources: JPL ZCS CLZ ZYH.Supervision: JPL ZCS.Validation: WZ XZ.Writing – original draft: WZ XZ JPL ZCS.Writing – review & editing: WZ XZ JPL ZCS.</notes><notes>Competing Interests: The authors have declared that no competing interests exist.</notes><abstract>"Perioceutics" including antimicrobial therapy and host modulatory therapy has emerged as a vital adjunctive treatment of periodontal disease. Melatonin level was significantly reduced in patients with periodontal diseases suggesting melatonin could be applied as a potential "perioceutics" treatment of periodontal diseases. This study aims to investigate the effects of melatonin receptor agonists (melatonin and ramelteon) on Porphyromonas gingivalis virulence and Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS)-induced inflammation.
Effects of melatonin receptor agonists on Porphyromonas gingivalis planktonic cultures were determined by microplate dilution assays. Formation, reduction, and viability of Porphyromonas gingivalis biofilms were detected by crystal violet staining and MTT assays, respectively. Meanwhile, biofilms formation was also observed by confocal laser scanning microscopy (CLSM). The effects on gingipains and hemolytic activities of Porphyromonas gingivalis were evaluated using chromogenic peptides and sheep erythrocytes. The mRNA expression of virulence and iron/heme utilization was assessed using RT-PCR. In addition, cell viability of melatonin receptor agonists on human gingival fibroblasts (HGFs) was evaluated by MTT assays. After pretreatment of melatonin receptor agonists, HGFs were stimulated with Pg-LPS and then release of cytokines (IL-6 and lL-8) was measured by enzyme-linked immunosorbent assay (ELISA).
Melatonin and ramelteon did exhibit antimicrobial effects against planktonic culture. Importantly, they inhibited biofilm formation, reduced the established biofilms, and decreased biofilm viability of Porphyromonas gingivalis. Furthermore, they at sub-minimum inhibitory concentration (sub-MIC) concentrations markedly inhibited the proteinase activities of gingipains and hemolysis in a dose-dependent manner. They at sub-MIC concentrations significantly inhibited the mRNA expression of virulence factors (kgp, rgpA, rgpB, hagA, and ragA), while increasing the mRNA expression of ferritin (ftn) or hemolysin (hem). They did not show obvious cytotoxicity toward HGFs. They inhibited Pg-LPS-induced IL-6 and IL-8 secretion, which was reversed by luzindole, the melatonin receptor antagonist.
Melatonin receptor agonists can inhibit planktonic and biofilm growth of Porphyromonas gingivalis by affecting the virulent properties, as well as Pg-LPS-induced inflammatory response. Our study provides new evidence that melatonin receptor agonists might be useful as novel "perioceutics" agents to prevent and treat Porphyromonas gingivalis-associated periodontal diseases.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27832188</pmid><doi>10.1371/journal.pone.0166442</doi><tpages>e0166442</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-11, Vol.11 (11), p.e0166442-e0166442 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1838211897 |
| source | Publicly Available Content Database; PubMed Central |
| subjects | Animals Anti-Bacterial Agents - pharmacology Anti-Inflammatory Agents - pharmacology Antiinfectives and antibacterials Antimicrobial agents Assaying Bacteria Biofilms Biofilms - drug effects Biology and Life Sciences Cell culture Cells, Cultured Confocal microscopy Cytokines Cytotoxicity Dilution Disease Diseases Enzyme-linked immunosorbent assay Enzymes Erythrocytes Ferritin Fibroblasts Fibroblasts - drug effects Fibroblasts - immunology Fibroblasts - microbiology Gene expression Gene Expression Regulation, Bacterial - drug effects Gum disease Heme Hemoglobin Hemolysis - drug effects Hospitals Humans Indenes - pharmacology Inflammation Inflammatory response Interleukin 6 Interleukin 8 Interleukin-6 - immunology Interleukin-8 - immunology Iron Laboratories Lipopolysaccharides Medical research Medical treatment Medicine Medicine and Health Sciences Melatonin Melatonin - pharmacology Microscopy Minimum inhibitory concentration Mitogens Pathogens Peptides Periodontal disease Periodontal diseases Periodontal Diseases - drug therapy Periodontal Diseases - immunology Polymerase chain reaction Porphyromonas gingivalis Porphyromonas gingivalis - drug effects Porphyromonas gingivalis - immunology Porphyromonas gingivalis - pathogenicity Porphyromonas gingivalis - physiology Proteinase Ragas Receptors, Melatonin - agonists RNA Sheep Studies Therapy Toxicity Virulence Virulence (Microbiology) Virulence factors |
| title | Melatonin Receptor Agonists as the "Perioceutics" Agents for Periodontal Disease through Modulation of Porphyromonas gingivalis Virulence and Inflammatory Response |
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