Epstein-Barr Virus Promotes the Production of Inflammatory Cytokines in Gingival Fibroblasts and RANKL-Induced Osteoclast Differentiation in RAW264.7 Cells

• Published in: International journal of molecular sciences 2022-01, Vol.23 (2), p.809
• Main Authors: Yokoe, Sho, Hasuike, Akira, Watanabe, Norihisa, Tanaka, Hideki, Karahashi, Hiroyuki, Wakuda, Shin, Takeichi, Osamu, Kawato, Takayuki, Takai, Hideki, Ogata, Yorimasa, Sato, Shuichi, Imai, Kenichi
• Format: Article
• Language: English
• Subjects: Animals; Bacteria; Bacterial infections; Biodegradation; Biomedical materials; Cell Differentiation; Cells, Cultured; Cytokines; Cytokines - genetics; Cytokines - metabolism; Cytomegalovirus; Differentiation (biology); Disease; E coli; Epstein-Barr virus; Epstein-Barr Virus Infections - metabolism; Epstein-Barr Virus Infections - virology; Etiology; Fibroblasts; Gene Expression; Gingiva - cytology; Gingiva - virology; Gum disease; Herpesvirus 4, Human - physiology; Host-Pathogen Interactions; Infections; Inflammation; Inflammation Mediators - metabolism; Interleukin 6; Interleukin 8; Kinases; Ligands; Lipopolysaccharides; Lipoteichoic acid; Macrophages; Mice; NF-κB protein; Osteoclastogenesis; Osteoclasts - metabolism; Pathogenesis; Periodontitis; Phosphorylation; Public health; RANK Ligand - metabolism; RAW 264.7 Cells; Signal Transduction; TRANCE protein; Transcription; Tumor necrosis factor-TNF; Viruses
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23020809

Periodontitis is an inflammatory condition that causes the destruction of the supporting tissues of teeth and is a major public health problem affecting more than half of the adult population worldwide. Recently, members of the herpes virus family, such as the Epstein-Barr virus (EBV), have been suggested to be involved in the etiology of periodontitis because bacterial activity alone does not adequately explain the clinical characteristics of periodontitis. However, the role of EBV in the etiology of periodontitis is unknown. This study aimed to examine the effect of inactivated EBV on the expression of inflammatory cytokines in human gingival fibroblasts (HGFs) and the induction of osteoclast differentiation. We found that extremely high levels of interleukin (IL)-6 and IL-8 were induced by inactivated EBV in a copy-dependent manner in HGFs. The levels of IL-6 and IL-8 in HGFs were higher when the cells were treated with EBV than when treated with lipopolysaccharide and lipoteichoic acid. EBV induced IκBα degradation, NF-κB transcription, and RAW264.7 cell differentiation into osteoclast-like cells. These findings suggest that even without infecting the cells, EBV contributes to inflammatory cytokine production and osteoclast differentiation by contact with oral cells or macrophage lineage, resulting in periodontitis onset and progression.