IADR Abstract Archives

Inhibitory effects of lactoferrin on LPS-induced crosstalk among TLR pathways

Objectives: The host immune response to pathogenic factors of periodontal pathogens has a crucial role in the periodontal tissue destruction in periodontal disease. Lipopolisaccharide (LPS) plays an important role in the pathogenesis and progress of periodontal disease through production of cytokines via Toll-like receptor (TLR) 4  pathway. Previously, we have demonstrated that bovine lactoferrin (bLF) inhibits LPS-induced bone destruction in rat and improves probing depth in patients with periodontitis. Recently, it was reported that crosstalk among TLRs plays important roles in inflammatory tissue destruction. The purpose of this study, therefore, is to investigate the inhibitory effects of bLF on LPS-induced crosstalk among TLR pathways in the periodontal tissue destruction.

Methods: Gene and protein expressions in periodontal tissue constituent cells were analyzed with RT-PCR and Western blot analysis, respectively. The expressions of TLRs in LPS-induced periodontal tissue destruction model of rats with or without oral administration of bLF were evaluated by immunohistochemical staining.

Results: In periodontal ligament cells, LPS up-regulated TLR5 and TLR9 expression and  the sensitivity of TLR5 and TLR9 to each ligands.  LPS, then, increased TNF-a production. The up-regulation of TLR5 and TLR9 expressions by LPS stimulation were also observed in osteoblasts and cementoblasts. bLF inhibited LPS-induced degradation of IkBa and phospholyration of p65, resulting in suppressing induction of TLR5 and TLR9. Moreover, bLF reduced LPS-induced TNF-a production and the expression of TLR5 and TLR9 in vivo experimental animals.

Conclusions: In the pathogenesis of periodontitis, LPS plays a central role among several pathogenic factors through affecting crosstalk of TLRs. We demonstrated that bLF inhibits LPS-induced crosstalk of TLRs and production of TNF-a by suppressing NFkB activation. Taken all together, bLF could be used as an effective agent against the destruction of alveolar bone induced by pathogenic factors in periodontitis.

Division: Japanese Division Meeting
Meeting: 2012 Japanese Division Meeting (Niigata, Japan)
Location: Niigata, Japan
Year: 2012
Final Presentation ID:
Abstract Category|Abstract Category(s): Scientific Program
Authors
  • Yanagisawa, Syunryo  ( Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, N/A, Japan )
  • Inubushi, Toshihiro  ( Hiroshima University, Hiroshima, N/A, Japan )
  • Miyauchi, Mutsumi  ( Hiroshima University, Hiroshima, N/A, Japan )
  • Furusho, Hisako  ( Hiroshima University, Hiroshima, N/A, Japan )
  • Ao, Min  ( Hiroshima University, Hiroshima, N/A, Japan )
  • Ishikado, Atsushi  ( Sunstar, Inc, Takatsuki, N/A, Japan )
  • Takata, Takashi  ( Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, N/A, Japan )
  • SESSION INFORMATION
    Periodontal Research