Gram-negative periodontal bacteria induce the activation of Toll-like receptors 2 and 4, and cytokine production in human periodontal ligament cells.
BACKGROUND
Periodontitis is a bacterially induced chronic inflammatory disease. Toll-like receptors (TLRs), which could recognize microbial pathogens, are important components in the innate and adaptive immune systems. Both qualitatively and quantitatively distinct immune responses might result from different bacteria stimulation and the triggering of different TLRs. This study explores the interaction of Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) with TLR2 and TLR4.


METHODS
We studied the gene expression changes of TLR2 and TLR4 and cytokine production (interleukin-1β, -6, -8, -10, and tumor necrosis factor-alpha) in human periodontal ligament cells (HPDLCs) stimulated with heat-killed bacteria or P. gingivalis lipopolysaccharide (LPS) in the presence or absence of monoclonal antibodies to TLR2 or TLR4 (anti-TLR2/4 mAb).


RESULTS
Both test bacteria and 10 microg/ml P. gingivalis LPS treatment increased the gene expression of TLR2 and TLR4 and cytokine production in HPDLCs. In addition, these upregulations could be blocked by anti-TLR2/4 mAb. However, the expression of TLR4 mRNA in HPDLCs stimulated with 1 microg/ml P. gingivalis LPS was not increased. No differences were found in the cytokine production caused by 1 microg/ml P. gingivalis LPS treatment in the presence or absence of anti-TLR4 mAb.


CONCLUSIONS
These patterns of gene expression and cytokine production indicate that Gram-negative periodontal bacteria or their LPS might play a role in triggering TLR2 and/or TLR4, and be of importance for the immune responses in periodontitis.
Sun
Ying
Y
Department of Periodontology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shu
Rong
R
Li
Chao-Lun
CL
Zhang
Ming-Zhu
MZ
D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D016967:Fusobacterium nucleatum / Q000276:immunology; D015870:Gene Expression; D006090:Gram-Negative Bacteria / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides; D010513:Periodontal Ligament / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D010518:Periodontitis / Q000276:immunology; D016966:Porphyromonas gingivalis / Q000276:immunology; D018713:Prevotella intermedia / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis* / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D000911:Antibodies, Monoclonal; D007378:Interleukins; D008070:Lipopolysaccharides; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha