scholarly journals Toll-Like Receptors Confer Responsiveness to Lipopolysaccharide from Porphyromonas gingivalis in Human Gingival Fibroblasts

2000 ◽  
Vol 68 (6) ◽  
pp. 3731-3735 ◽  
Author(s):  
Kouich Tabeta ◽  
Kazuhisa Yamazaki ◽  
Sachiko Akashi ◽  
Kensuke Miyake ◽  
Hidefumi Kumada ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Proinflammatory Cytokines ◽  
Interleukin 6 ◽  
Intracellular Signaling ◽  
Myeloid Cells ◽  
Human Gingival Fibroblasts ◽  
Gingival Fibroblasts ◽  
Toll Like Receptors ◽  
Human Homologue ◽  
Periodontopathic Bacteria

ABSTRACT Gingival fibroblasts produce proinflammatory cytokines in response to lipopolysaccharide (LPS) from periodontopathic bacteria. Recently it has become evident that the human homologue of DrosophilaToll can transduce intracellular signaling by LPS stimulation. Toll-like receptors (TLRs) have been identified in myeloid cells; however, their role in nonmyeloid cells such as gingival fibroblasts has not been fully elucidated. Here, we report that human gingival fibroblasts constitutively express TLR2 and TLR4 and that their levels of expression are increased by stimulation with LPS fromPorphyromonas gingivalis. Upregulated expression of interleukin-6 gene and protein in fibroblasts stimulated with LPS is inhibited by anti-TLR4 antibody. These findings suggest that TLRs may confer responsiveness to LPS in gingival fibroblasts.

scholarly journals CpG Motifs in Porphyromonas gingivalis DNA Stimulate Interleukin-6 Expression in Human Gingival Fibroblasts

1999 ◽  
Vol 67 (9) ◽  
pp. 4340-4345 ◽  
Author(s):  
Akira Takeshita ◽  
Kenichi Imai ◽  
Shigemasa Hanazawa
Keyword(s):  
Porphyromonas Gingivalis ◽  
Interleukin 6 ◽  
Consensus Sequence ◽  
Human Gingival Fibroblasts ◽  
Pyrrolidine Dithiocarbamate ◽  
Dependent Manner ◽  
Gingival Fibroblasts ◽  
Bacterial Dna ◽  
Synthetic Oligonucleotide ◽  
Cpg Motifs

ABSTRACT We suggest here that Porphyromonas gingivalis DNA may function as a virulence factor in periodontal disease through expression of inflammatory cytokine. The bacterial DNA markedly stimulated in a dose-dependent manner interleukin-6 (IL-6) production by human gingival fibroblasts. The stimulatory action was eliminated by treatment with DNase but not RNase. The stimulatory effect was not observed in the fibroblasts treated with eucaryotic DNAs. The bacterial DNA also stimulated in dose- and treatment time-dependent manners the expression of the IL-6 gene in the cells. In addition, the stimulatory effect was eliminated when the DNA was methylated with CpG motif methylase. Interestingly, a 30-base synthetic oligonucleotide containing the palindromic motif GACGTC could stimulate expression of the IL-6 gene and production of its protein in the cells. Furthermore, the synthetic oligonucleotide-induced expression of this cytokine gene was blocked by pyrrolidine dithiocarbamate andN-acetyl-l-cystine, potent inhibitors of transcriptional factor NF-κB. Gel mobility shift assay showed increased binding of NF-κB to its consensus sequence in the synthetic oligonucleotide-treated cells. Also, using specific antibody against p50 and p65, which compose NF-κB, we showed the consensus sequence-binding proteins to be NF-κB. These results are the first to demonstrate that the internal CpG motifs in P. gingivalisDNA stimulate IL-6 expression in human gingival fibroblasts via stimulation of NF-κB.

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