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Conference Paper: Porphyromonas gingivalis LPS regulates MnSOD in HGFs through TLR4-NF-κB pathway

TitlePorphyromonas gingivalis LPS regulates MnSOD in HGFs through TLR4-NF-κB pathway
Authors
KeywordsFibroblasts
Gene expression
Host-microbial interactions
Infection and Periodontal disease
Issue Date2012
PublisherSage Publications, Inc.. The Journal's web site is located at http://www.sagepub.com/journalsProdDesc.nav?prodId=Journal201925
Citation
The Annual Meeting of the International Association for Dental Research (IADR) Southeast Asian Division, Hong Kong, China, 3-4 November 2012. In Journal of Dental Research, 2012, v. 91 n. Special Issue C: abstract no. 169737 How to Cite?
AbstractObjectives: Porphyromonas gingivalis is a keystone periodontal pathogen and its lipopolysacharide (LPS) is strongly associated with periodontal disease. P. gingivalis LPS (PgLPS) displays remarkable heterogeneity containing both tetra- (LPS1435/1449) and penta-acylated (LPS1690) lipid A structures. We recently demonstrated that PgLPS differentially modulates the immuno-inflammatory response in human gingival fibroblasts (HGFs). The present study further investigated the expression and regulation of antioxidants in HGFs in response to heterogeneous PgLPS. Methods: Primary HGFs were treated with PgLPS1435/1449 and PgLPS1690 as well as E. coli LPS in appropriate dose- and time-dependent assays. Modulation of oxidative stress and anti-oxidant defense pathways were examined using gene-expression arrays. The identified biomarkers were further validated by real-time qPCR and Western blot. Involvement of TLRs and signaling pathways (MAPK/NF-κB) for PgLPS-induced MnSOD expression was elucidated by Western blot and antibody-mediated blocking assays. Results: Gene-array results showed that PgLPS1690 upregulated significantly the antioxidants MnSOD (SOD2), SOD3 and PXDNL compared to the PgLPS1435/1449. PgLPS1690 and E. coli LPS significantly upregulates MnSOD, PRDX1 and TXN1 mRNAs in dose- and time-dependent manners. MnSOD mRNA expression was significantly inhibited in PgLPS1690-treated cells through NF-κB and SAPK/JNK pathways. In contrast, blockage of NF-κB and P38 MAPK significantly inhibited MnSOD expression in E. coli LPS-treated cells. Both TLR4 and TLR2 were involved in the regulation of MnSOD expression in PgLPS1690-treated HGFs, whereas only TLR4 was involved in E. coli LPS-treated HGFs. Conclusions: This study unravels for the first time the oxidative stress and antioxidant expression of HGFs in response to heterogeneous PgLPS. MnSOD could play a key role in antioxidant defense of gingival tissues through TLRs and NF-κB signaling pathway by targeting P. gingivalis to shift its LPS structure, which could be a strategy to restore the antioxidant status of gingival tissues and thereby preventing periodontal diseases. (Supported by the Hong Kong RGC, No. HKU766909M).
DescriptionSession: Periodontal Research
Persistent Identifierhttp://hdl.handle.net/10722/182061
ISSN
2015 Impact Factor: 4.602
2015 SCImago Journal Rankings: 1.714

 

DC FieldValueLanguage
dc.contributor.authorHerath, MTDKHen_US
dc.contributor.authorWang, Yen_US
dc.contributor.authorSeneviratne, CJen_US
dc.contributor.authorDarveau, RPen_US
dc.contributor.authorWang, CYen_US
dc.contributor.authorJin, Len_US
dc.date.accessioned2013-04-17T07:20:43Z-
dc.date.available2013-04-17T07:20:43Z-
dc.date.issued2012en_US
dc.identifier.citationThe Annual Meeting of the International Association for Dental Research (IADR) Southeast Asian Division, Hong Kong, China, 3-4 November 2012. In Journal of Dental Research, 2012, v. 91 n. Special Issue C: abstract no. 169737en_US
dc.identifier.issn0022-0345en_US
dc.identifier.urihttp://hdl.handle.net/10722/182061-
dc.descriptionSession: Periodontal Research-
dc.description.abstractObjectives: Porphyromonas gingivalis is a keystone periodontal pathogen and its lipopolysacharide (LPS) is strongly associated with periodontal disease. P. gingivalis LPS (PgLPS) displays remarkable heterogeneity containing both tetra- (LPS1435/1449) and penta-acylated (LPS1690) lipid A structures. We recently demonstrated that PgLPS differentially modulates the immuno-inflammatory response in human gingival fibroblasts (HGFs). The present study further investigated the expression and regulation of antioxidants in HGFs in response to heterogeneous PgLPS. Methods: Primary HGFs were treated with PgLPS1435/1449 and PgLPS1690 as well as E. coli LPS in appropriate dose- and time-dependent assays. Modulation of oxidative stress and anti-oxidant defense pathways were examined using gene-expression arrays. The identified biomarkers were further validated by real-time qPCR and Western blot. Involvement of TLRs and signaling pathways (MAPK/NF-κB) for PgLPS-induced MnSOD expression was elucidated by Western blot and antibody-mediated blocking assays. Results: Gene-array results showed that PgLPS1690 upregulated significantly the antioxidants MnSOD (SOD2), SOD3 and PXDNL compared to the PgLPS1435/1449. PgLPS1690 and E. coli LPS significantly upregulates MnSOD, PRDX1 and TXN1 mRNAs in dose- and time-dependent manners. MnSOD mRNA expression was significantly inhibited in PgLPS1690-treated cells through NF-κB and SAPK/JNK pathways. In contrast, blockage of NF-κB and P38 MAPK significantly inhibited MnSOD expression in E. coli LPS-treated cells. Both TLR4 and TLR2 were involved in the regulation of MnSOD expression in PgLPS1690-treated HGFs, whereas only TLR4 was involved in E. coli LPS-treated HGFs. Conclusions: This study unravels for the first time the oxidative stress and antioxidant expression of HGFs in response to heterogeneous PgLPS. MnSOD could play a key role in antioxidant defense of gingival tissues through TLRs and NF-κB signaling pathway by targeting P. gingivalis to shift its LPS structure, which could be a strategy to restore the antioxidant status of gingival tissues and thereby preventing periodontal diseases. (Supported by the Hong Kong RGC, No. HKU766909M).-
dc.languageengen_US
dc.publisherSage Publications, Inc.. The Journal's web site is located at http://www.sagepub.com/journalsProdDesc.nav?prodId=Journal201925en_US
dc.relation.ispartofJournal of Dental Researchen_US
dc.rightsJournal of Dental Research. Copyright © Sage Publications, Inc..en_US
dc.subjectFibroblasts-
dc.subjectGene expression-
dc.subjectHost-microbial interactions-
dc.subjectInfection and Periodontal disease-
dc.titlePorphyromonas gingivalis LPS regulates MnSOD in HGFs through TLR4-NF-κB pathwayen_US
dc.typeConference_Paperen_US
dc.identifier.emailWang, Y: yuwanghk@hku.hken_US
dc.identifier.emailSeneviratne, CJ: jaya@hku.hken_US
dc.identifier.emailJin, L: ljjin@hkucc.hku.hken_US
dc.identifier.authorityWang, Y=rp00239en_US
dc.identifier.authoritySeneviratne, CJ=rp01372en_US
dc.identifier.authorityJin, L=rp00028en_US
dc.identifier.hkuros213909en_US
dc.identifier.volume91en_US
dc.identifier.issueSpecial Issue C: abstract no. 169737en_US
dc.publisher.placeUnited States-

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