title: 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.
authors.affiliation: Periodontology, Bio-Matrix Department, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Misa
authors.initials: M
authors.lastname: Gokyu
authors.affiliation: Periodontology, Bio-Matrix Department, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Periodontology, Bio-Matrix Department, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nanbara
authors.affiliation: Periodontology, Bio-Matrix Department, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Takeaki
authors.initials: T
authors.lastname: Sudo
authors.affiliation: Periodontology, Bio-Matrix Department, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Periodontology, Bio-Matrix Department, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Suda
authors.affiliation: Periodontology, Bio-Matrix Department, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Izumi
mesh_terms: D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D046228:Microarray Analysis; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D010518:Periodontitis / Q000378:metabolism* / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D019700:Thrombospondin 1 / Q000096:biosynthesis* / Q000235:genetics; D051193:Toll-Like Receptors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D052002:NF-kappa B p50 Subunit; D012333:RNA, Messenger; D019700:Thrombospondin 1; D051193:Toll-Like Receptors