File Download

Conference Paper: Novel pathogenic mechanisms of heterogeneous PG-LPS structures in periodontal disease

TitleNovel pathogenic mechanisms of heterogeneous PG-LPS structures in periodontal disease
Authors
KeywordsHost-microbial interactions
Inflammatory mediators
Periodontal disease
Issue Date2011
PublisherThe International Association for Dental Research.
Citation
The 25th Annual Scientific Meeting of the IADR-SEA Division and the 22nd Annual Meeting of SEAADE, Singapore, 28-30 October 2011. How to Cite?
AbstractOBJECTIVE: Porphyromonas gingivalis lipopolysaccharide (PgLPS) displays significant amount of lipid-A heterogeneity, containing both tetra (LPS1435/1449) and penta-acylated (LPS1690) isoforms. We recently demonstrated PgLPS isoforms differentially modulate the immuno-inflammatory response in human gingival fibroblasts (HGFs). This study aimed to unravel the molecular mechanism by which PgLPS regulates the immuno-inflammatory activity, lipid peroxidation and apoptotic pathways in HGFs. METHODS: Primary HGFs were treated with PgLPS1435/1449 and PgLPS1690 in both dose-dependent and time-dependent experiments. Modulation of lipid peroxidation and apoptotic pathways was examined using gene-expression arrays and validated by qPCR and western blot. Antibody blocking assays were performed for TLRs (TLR2/TLR4) and signal transduction pathways (MAPK/NF-kB) to determine the mechanisms of PgLPS-HGFs interactions. Down-stream markers related to immuno-inflammatory response were examined by qPCR, ELISA and western blot. RESULTS: PgLPS1690 up-regulated anti-oxidant molecules like thioredoxin and superoxide dismutase, whereas PgLPS1435/1449 down-regulated the expression of these molecules in a time-dependent manner. In contrast to PgLPS1435/1449, apoptosis pathway molecules such as caspases 3, 5, 8 and 9 were induced by PgLPS1690. PgLPS1690 induced chemokines CCL2, CXCL10 and GM-CSF. Interestingly, PgLPS utilized different mechanisms (TLRs related signal transduction pathways) in modulating host innate response, which could account for aforementioned observations. CONCLUSIONS: This study unraveled for the first time the molecular mechanisms of heterogeneous PgLPS isoforms to disguise host immune response for Pg survival and proliferation in gingival tissues. The current findings may contribute to the development of novel strategies for controlling periodontal diseases (Supported by Hong Kong Research Grants Council, GRF No. HKU766909M to LJJ).
DescriptionPoster Discussion Session: 16. Senior Researcher Division Travel Award: paper no. 82
Persistent Identifierhttp://hdl.handle.net/10722/143828

 

DC FieldValueLanguage
dc.contributor.authorHerath, Ten_US
dc.contributor.authorWang, Yen_US
dc.contributor.authorSeneviratne, Cen_US
dc.contributor.authorDarveau, Ren_US
dc.contributor.authorWang, Cen_US
dc.contributor.authorJin, Len_US
dc.date.accessioned2011-12-21T08:56:56Z-
dc.date.available2011-12-21T08:56:56Z-
dc.date.issued2011en_US
dc.identifier.citationThe 25th Annual Scientific Meeting of the IADR-SEA Division and the 22nd Annual Meeting of SEAADE, Singapore, 28-30 October 2011.en_US
dc.identifier.urihttp://hdl.handle.net/10722/143828-
dc.descriptionPoster Discussion Session: 16. Senior Researcher Division Travel Award: paper no. 82-
dc.description.abstractOBJECTIVE: Porphyromonas gingivalis lipopolysaccharide (PgLPS) displays significant amount of lipid-A heterogeneity, containing both tetra (LPS1435/1449) and penta-acylated (LPS1690) isoforms. We recently demonstrated PgLPS isoforms differentially modulate the immuno-inflammatory response in human gingival fibroblasts (HGFs). This study aimed to unravel the molecular mechanism by which PgLPS regulates the immuno-inflammatory activity, lipid peroxidation and apoptotic pathways in HGFs. METHODS: Primary HGFs were treated with PgLPS1435/1449 and PgLPS1690 in both dose-dependent and time-dependent experiments. Modulation of lipid peroxidation and apoptotic pathways was examined using gene-expression arrays and validated by qPCR and western blot. Antibody blocking assays were performed for TLRs (TLR2/TLR4) and signal transduction pathways (MAPK/NF-kB) to determine the mechanisms of PgLPS-HGFs interactions. Down-stream markers related to immuno-inflammatory response were examined by qPCR, ELISA and western blot. RESULTS: PgLPS1690 up-regulated anti-oxidant molecules like thioredoxin and superoxide dismutase, whereas PgLPS1435/1449 down-regulated the expression of these molecules in a time-dependent manner. In contrast to PgLPS1435/1449, apoptosis pathway molecules such as caspases 3, 5, 8 and 9 were induced by PgLPS1690. PgLPS1690 induced chemokines CCL2, CXCL10 and GM-CSF. Interestingly, PgLPS utilized different mechanisms (TLRs related signal transduction pathways) in modulating host innate response, which could account for aforementioned observations. CONCLUSIONS: This study unraveled for the first time the molecular mechanisms of heterogeneous PgLPS isoforms to disguise host immune response for Pg survival and proliferation in gingival tissues. The current findings may contribute to the development of novel strategies for controlling periodontal diseases (Supported by Hong Kong Research Grants Council, GRF No. HKU766909M to LJJ).-
dc.languageengen_US
dc.publisherThe International Association for Dental Research.-
dc.relation.ispartofIADR/SEAADE Annual Scientific Meeting, 2011en_US
dc.subjectHost-microbial interactions-
dc.subjectInflammatory mediators-
dc.subjectPeriodontal disease-
dc.titleNovel pathogenic mechanisms of heterogeneous PG-LPS structures in periodontal diseaseen_US
dc.typeConference_Paperen_US
dc.identifier.emailHerath, T: thanuja@HKUSUC.hku.hken_US
dc.identifier.emailWang, Y: yuwanghk@hku.hken_US
dc.identifier.emailSeneviratne, C: jaya@hku.hken_US
dc.identifier.emailJin, L: ljjin@hkucc.hku.hk-
dc.identifier.authorityWang, Y=rp00239en_US
dc.identifier.authoritySeneviratne, C=rp01372en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros197881en_US
dc.publisher.placeUnited States-
dc.description.otherThe 25th Annual Scientific Meeting of the IADR-SEA Division and the 22nd Annual Meeting of SEAADE, Singapore, 28-30 October 2011.-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats