Thrombospondin-1 Production Is Enhanced by Porphyromonas gingivalis Lipopolysaccharide in THP-1 Cells

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.

A complex interplay between the extracellular matrix and the innate immune response to microbial pathogens

“…Moreover, bacterial components induce tenascin‐C expression in human monocyte‐derived and mouse bone‐marrow‐derived macrophages . Lipopolysaccharide from Porphyromonas gingivalis induces thrombospondin‐1 production in THP‐1 cells, while LPS from Escherichia coli and IFN‐ γ up‐regulate galectin‐1 and galectin‐3, including five galectin‐3 truncated forms, in primary human macrophages . In mice with viral myocarditis, macrophages infiltrating the heart are the main producers of osteopontin .…”

The role of Toll‐like receptors in periodontitis

“…Thrombospondin‐1 (TSP‐1) has been associated with some systemic diseases, including RA (Rico et al , ; Ohyama et al , ) and DM (Choi et al , ; Wang et al , ). Gokyu et al () found that after THP‐1 cells were stimulated with LPS from Porphyromonas gingivalis , the gene expression of TSP‐1 was markedly elevated via the TLR2‐mediated NF‐ κ B pathway, indicating that TLR2 might be involved in TSP‐1 production that could exacerbate RA or DM. Based on this study, TLR2 has been suggested as a potential therapeutic target in the treatment of PD, RA, and DM.…”

The Role of Clinical Proteomics, Lipidomics, and Genomics in the Diagnosis of Alzheimer’s Disease

“…Zinc is sensitive to HNF4 [187] and reduced hepatic TNF-α toxicity [188,189] may aid the prevention of insulin resistance and AD [1]. Nutriproteomic diets as a treatment for reduction of LPS effects may lower TSP-1 expression by peripheral cells [190,191,192] and improve peripheral LPS–protein interactions [193,194,195,196] to accelerate peripheral amyloid beta metabolism with respect to treatment of individuals with prodromal disease and dementia. Nutritional diets that activate Sirt 1 and maintain therapeutic VIP and FGF21 levels [51] accelerate hepatic LPS/mycotoxin metabolism without transfer to the CSF and brain compartment [21], which is consistent with the use of nutritional therapy to maintain CSF composition, recycling, and amyloid beta dynamics [197,198] for the prevention of early neurodegeneration (stages 1–3) and amyloidosis.…”