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Thrombospondin-1 production is enhanced by Porphyromonas gingivalis lipopolysaccharide in THP-1 cells.

Gokyu M, Kobayashi H, Nanbara H, Sudo T, Ikeda Y, Suda T, Izumi Y - PLoS ONE (2014)

Bottom Line: Recent studies have suggested that TSP-1 is associated with rheumatoid arthritis, diabetes mellitus, and osteoclastogenesis.Furthermore, IL-17F synergistically enhanced P. gingivalis LPS-induced TSP-1 production.It may also contribute a new target molecule for periodontal therapy.

View Article: PubMed Central - PubMed

Affiliation: Periodontology, Bio-Matrix Department, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

ABSTRACT
Periodontitis is a chronic inflammatory disease caused by gram-negative anaerobic bacteria. Monocytes and macrophages stimulated by periodontopathic bacteria induce inflammatory mediators that cause tooth-supporting structure destruction and alveolar bone resorption. In this study, using a DNA microarray, we identified the enhanced gene expression of thrombospondin-1 (TSP-1) in human monocytic cells stimulated by Porphyromonas gingivalis lipopolysaccharide (LPS). TSP-1 is a multifunctional extracellular matrix protein that is upregulated during the inflammatory process. Recent studies have suggested that TSP-1 is associated with rheumatoid arthritis, diabetes mellitus, and osteoclastogenesis. TSP-1 is secreted from neutrophils, monocytes, and macrophages, which mediate immune responses at inflammatory regions. However, TSP-1 expression in periodontitis and the mechanisms underlying TSP-1 expression in human monocytic cells remain unknown. Here using real-time RT-PCR, we demonstrated that TSP-1 mRNA expression level was significantly upregulated in inflamed periodontitis gingival tissues and in P. gingivalis LPS-stimulated human monocytic cell line THP-1 cells. TSP-1 was expressed via Toll-like receptor (TLR) 2 and TLR4 pathways. In P. gingivalis LPS stimulation, TSP-1 expression was dependent upon TLR2 through the activation of NF-κB signaling. Furthermore, IL-17F synergistically enhanced P. gingivalis LPS-induced TSP-1 production. These results suggest that modulation of TSP-1 expression by P. gingivalis plays an important role in the progression and chronicity of periodontitis. It may also contribute a new target molecule for periodontal therapy.

No MeSH data available.


Related in: MedlinePlus

The level of TSP-1 mRNA expression was significantly upregulated in periodontitis gingival tissues.Human gingival tissues were obtained from periodontal surgical operations. TSP-1 mRNA expression was enhanced in inflammatory gingival tissues. Its expression was significantly higher in regions of deep periodontal pockets than in shallow periodontal pockets and healthy sites (P<0.001).
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pone-0115107-g001: The level of TSP-1 mRNA expression was significantly upregulated in periodontitis gingival tissues.Human gingival tissues were obtained from periodontal surgical operations. TSP-1 mRNA expression was enhanced in inflammatory gingival tissues. Its expression was significantly higher in regions of deep periodontal pockets than in shallow periodontal pockets and healthy sites (P<0.001).

Mentions: The level of TSP-1 mRNA expression was significantly upregulated in the deep periodontal pocket gingiva group (PPD ≥4 mm) compared with that in the shallow periodontal pocket gingiva (PPD <4 mm) and no inflammatory gingiva groups (Healthy; Fig. 1). PPD was 5.6±1.5 mm (mean ± SD) in the Deep periodontal pocket group and 2.4±0.5 mm in the Shallow periodontal pocket group. Between these two groups, a 2-tailed P value of <0.0001 was considered extremely significant. There was a tendency for increased production of TSP-1 mRNA as the periodontal pocket became deeper.


Thrombospondin-1 production is enhanced by Porphyromonas gingivalis lipopolysaccharide in THP-1 cells.

Gokyu M, Kobayashi H, Nanbara H, Sudo T, Ikeda Y, Suda T, Izumi Y - PLoS ONE (2014)

The level of TSP-1 mRNA expression was significantly upregulated in periodontitis gingival tissues.Human gingival tissues were obtained from periodontal surgical operations. TSP-1 mRNA expression was enhanced in inflammatory gingival tissues. Its expression was significantly higher in regions of deep periodontal pockets than in shallow periodontal pockets and healthy sites (P<0.001).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264871&req=5

pone-0115107-g001: The level of TSP-1 mRNA expression was significantly upregulated in periodontitis gingival tissues.Human gingival tissues were obtained from periodontal surgical operations. TSP-1 mRNA expression was enhanced in inflammatory gingival tissues. Its expression was significantly higher in regions of deep periodontal pockets than in shallow periodontal pockets and healthy sites (P<0.001).
Mentions: The level of TSP-1 mRNA expression was significantly upregulated in the deep periodontal pocket gingiva group (PPD ≥4 mm) compared with that in the shallow periodontal pocket gingiva (PPD <4 mm) and no inflammatory gingiva groups (Healthy; Fig. 1). PPD was 5.6±1.5 mm (mean ± SD) in the Deep periodontal pocket group and 2.4±0.5 mm in the Shallow periodontal pocket group. Between these two groups, a 2-tailed P value of <0.0001 was considered extremely significant. There was a tendency for increased production of TSP-1 mRNA as the periodontal pocket became deeper.

Bottom Line: Recent studies have suggested that TSP-1 is associated with rheumatoid arthritis, diabetes mellitus, and osteoclastogenesis.Furthermore, IL-17F synergistically enhanced P. gingivalis LPS-induced TSP-1 production.It may also contribute a new target molecule for periodontal therapy.

View Article: PubMed Central - PubMed

Affiliation: Periodontology, Bio-Matrix Department, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

ABSTRACT
Periodontitis is a chronic inflammatory disease caused by gram-negative anaerobic bacteria. Monocytes and macrophages stimulated by periodontopathic bacteria induce inflammatory mediators that cause tooth-supporting structure destruction and alveolar bone resorption. In this study, using a DNA microarray, we identified the enhanced gene expression of thrombospondin-1 (TSP-1) in human monocytic cells stimulated by Porphyromonas gingivalis lipopolysaccharide (LPS). TSP-1 is a multifunctional extracellular matrix protein that is upregulated during the inflammatory process. Recent studies have suggested that TSP-1 is associated with rheumatoid arthritis, diabetes mellitus, and osteoclastogenesis. TSP-1 is secreted from neutrophils, monocytes, and macrophages, which mediate immune responses at inflammatory regions. However, TSP-1 expression in periodontitis and the mechanisms underlying TSP-1 expression in human monocytic cells remain unknown. Here using real-time RT-PCR, we demonstrated that TSP-1 mRNA expression level was significantly upregulated in inflamed periodontitis gingival tissues and in P. gingivalis LPS-stimulated human monocytic cell line THP-1 cells. TSP-1 was expressed via Toll-like receptor (TLR) 2 and TLR4 pathways. In P. gingivalis LPS stimulation, TSP-1 expression was dependent upon TLR2 through the activation of NF-κB signaling. Furthermore, IL-17F synergistically enhanced P. gingivalis LPS-induced TSP-1 production. These results suggest that modulation of TSP-1 expression by P. gingivalis plays an important role in the progression and chronicity of periodontitis. It may also contribute a new target molecule for periodontal therapy.

No MeSH data available.


Related in: MedlinePlus