[Effect of high mobility group box 1 (HMGB1) in cultured human periodontal ligament cells].

Abstract

The periodontal ligament (PDL) is a fibrous connective tissue that exists in the cementum and the alveolar bone. Periodontitis is a chronic inflammatory disease that is caused by a bacterial infection in the periodontal region. This infection increases the production of inflammatory cytokines and causes the destruction of periodontal tissue. High mobility group box 1 (HMGB1) is a nuclear nonhiston DNA-binding protein that is present in many eukaryotic cells. HMGB1 is released actively from macrophages and monocytes stimulated by lipopolysaccharide or tumor necrosis factor-alpha and passively from damaged cells and necrotic cells. Extracellular HMGB1 signals through a specialized receptor for advanced glycation end products (RAGE), toll-like receptor 2 (TLR2), and toll-like receptor 4 (TLR4). According to a recent report, HMGB1 is of concern in periodontitis. The purpose of this study was to examine the effect of HMGB1 in PDL cells. To investigate RAGE, TLR2 and TLR4 mRNA in PDL cells, reverse transcript-polymerase chain reaction experiments were performed. PDL cells were stimulated with HMGB1, with or without anti-RAGE, TLR2 and TLR4 antibodies. IL-6 and IL-11 production was measured using an enzyme-linked immunosorbent assay, and mRNA expression was quantified by real-time PCR. PDL cells expressed RAGE, TLR2 and TLR4 mRNA. Production and mRNA expression of IL-6 and IL-11 were augmented in PDL cells stimulated with HMGB1. In addition, they were also suppressed by anti-RAGE, TLR2 and TLR4 antibodies. In conclusion, PDL cells produce IL-6 and IL-11 in response to HMGB1 via RAGE, TLR2 and TLR4.