Induction of Toll‐Like Receptor Expression by Porphyromonas gingivalis

Abstract

Background: Toll‐like receptors (TLRs) play pivotal roles in host immune responses and have been suggested to be involved in the development of many infectious diseases. In this study, the mRNA expression levels of TLR2, TLR4, and TLR9 and their relationship with periodontopathic bacteria in periodontal tissue are examined. Furthermore, the mechanism of TLR induction by Porphyromonas gingivalis is investigated in human gingival fibroblasts (HGFs).Methods: Gingival tissue and subgingival plaque samples were collected from 19 patients with chronic periodontitis (CP) and 16 control individuals without periodontitis. Gene expression levels in the tissues and in HGFs were analyzed by reverse transcription‐polymerase chain reaction (RT‐PCR). The numbers of periodontopathic bacteria were determined by quantitative real‐time PCR.Results: The expression levels of TLR2 and TLR9 were significantly higher in the tissues of patients with CP compared to the tissues of control individuals. The mRNA levels of TLR2 and TLR9, but not TLR4, were positively correlated with the number of P. gingivalis in subgingival plaque. P. gingivalis sonicated extract, P. gingivalis lipopolysaccharide, P. gingivalis DNA, and tumor necrosis factor‐α(TNF‐α) could significantly upregulate the mRNA expression of TLR2 in HGFs. Furthermore, P. gingivalis–mediated TLR2 expression was suppressed by TNF‐α antibody.Conclusions: This study suggests that P. gingivalis infection induces TLR2 and TLR9 upregulation in patients with CP. P. gingivalis–induced TLR2 expression in HGFs is partially dependent on TNF‐α and may lead to sensitization of HGFs to bacterial components encountered in the periodontal microenvironment.

Different effects ofP. gingivalisLPS andE. coliLPS on the expression of interleukin-6 in human gingival fibroblasts

“…Particularly, Wang et al [14], using flow cytometry, showed that P. gingivalis LPS decreases the surface expression of TLR4 in GFs. Studies using real-time PCR show that the mRNA expression level of TLR2 and TLR4 is up-regulated by both P. gingivalis LPS [39,40] and E. coli LPS [41]. The controversy in the existing data could be explained by the heterogeneous structure of P. gingivalis LPS.…”

Toll-Like Receptor 9-Mediated Inflammation Triggers Alveolar Bone Loss in Experimental Murine Periodontitis

“…Recently, both our group and others revealed differential expression of specific single-nucleotide polymorphisms (SNPs) in the TLR9 gene in individuals with chronic periodontitis, providing further evidence for the involvement of TLR9 in periodontal disease (18,19). Additionally, in vitro investigations demonstrated that periodontitis-associated bacterial DNA upregulates several genes of the innate immune response and induces the production of proinflammatory cytokines through TLR9 in macrophages and epithelial cells (20)(21)(22). In fact, a recent study has identified the TLR9 gene as one of the most promising candidate genes involved in the pathogenesis of periodontitis by using an integrative gene prioritization method (23).…”

The Role of TLRs in the Pathogenesis of Periodontal Diseases

“…The mRNA levels of TLR2 and TLR9, but not TLR4, were positively correlated with the number of P. gingivalisin subgingival plaque. This study suggests that P. gingivalisinfection induces TLR2 and TLR9 upregulation in patients with periodontitis [33].Moreover,statistically significant upregulation of TLR9 and TLR8 have been reported in chronic periodontitis tissues compared to healthy sites [34]. In another study, gingival tissue samples were obtained from eight chronic periodontitis and nine gingivitis (3 mild; 3 moderate; 3 severe) patients.…”