title: Enterococcus faecalis lipoteichoic acid suppresses Aggregatibacter actinomycetemcomitans lipopolysaccharide-induced IL-8 expression in human periodontal ligament cells.
abstract: Periodontitis is caused by multi-bacterial infection and Aggregatibacter actinomycetemcomitans and Enterococcus faecalis are closely associated with inflammatory periodontal diseases. Although lipopolysaccharide (LPS) of A. actinomycetemcomitans (Aa.LPS) and lipoteichoic acid of E. faecalis (Ef.LTA) are considered to be major virulence factors evoking inflammatory responses, their combinatorial effect on the induction of chemokines has not been investigated. In this study, we investigated the interaction between Aa.LPS and Ef.LTA on IL-8 expression in human periodontal ligament (PDL) cells. Aa.LPS, but not Ef.LTA, substantially induced IL-8 expression at the protein and mRNA levels. Interestingly, Ef.LTA suppressed Aa.LPS-induced IL-8 expression without affecting the binding of Aa.LPS to Toll-like receptor (TLR) 4. Ef.LTA reduced Aa.LPS-induced phosphorylation of mitogen-activated protein kinases, including ERK, JNK and p38 kinase. Furthermore, Ef.LTA inhibited the Aa.LPS-induced transcriptional activities of the activating protein 1, CCAAT/enhancer-binding protein and nuclear factor-kappa B transcription factors, all of which are known to regulate IL-8 gene expression. Ef.LTA augmented the expression of IL-1 receptor-associated kinase-M (IRAK-M), a negative regulator of TLR intracellular signaling pathways, in the presence of Aa.LPS at both the mRNA and protein levels. Small interfering RNA silencing IRAK-M reversed the attenuation of Aa.LPS-induced IL-8 expression by Ef.LTA. Collectively, these results suggest that Ef.LTA down-regulates Aa.LPS-induced IL-8 expression in human PDL cells through up-regulation of the negative regulator IRAK-M.
authors.affiliation: Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Jintaek
authors.initials: J
authors.lastname: Im
authors.affiliation: Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Baik
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Kyoung Whun
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Seok-Seong
authors.initials: SS
authors.lastname: Kang
authors.affiliation: Division of High-risk Pathogen Research, Center for Infectious Diseases, Korea National Institute of Health, Osong 363-951, Republic of Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Jeon
authors.affiliation: Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Ok-Jin
authors.initials: OJ
authors.lastname: Park
authors.affiliation: Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Hyun Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Conservative Dentistry and DRI, School of Dentistry, Seoul National University, Seoul 110-768, Republic of Korea.
authors.forename: Kee-Yeon
authors.initials: KY
authors.lastname: Kum
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
authors.affiliation: Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea shhan-mi@snu.ac.kr.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Han
mesh_terms: D000328:Adult; D016976:Aggregatibacter actinomycetemcomitans / Q000737:chemistry* / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000276:immunology; D013293:Enterococcus faecalis / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000276:immunology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D010766:Phosphorylation; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013682:Teichoic Acids / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D016209:Interleukin-8; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; C495345:TLR4 protein, human; D013682:Teichoic Acids; D051197:Toll-Like Receptor 4; D018808:Transcription Factor AP-1; C009900:lipoteichoic acid; C507771:IRAK3 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
keywords: Aggregatibacter actinomycetemcomitans; Enterococcus faecalis; Interleukin-1 receptor–associated kinase-M; Interleukin-8; lipopolysaccharide; lipoteichoic acid; periodontal ligament cells