Norihisa Watanabe1,2, Keiko Nodomi2, Ryo Koike2,3, Ayako Kato4, Osamu Takeichi5, A I Kotani6, Tadayoshi Kaneko3, Hiroshi Sakagami7, Masami Takei8, Yorimasa Ogata4, Shuichi Sato1, Kenichi Imai9. 1. Department of Periodontology, Nihon University School of Dentistry, Tokyo, Japan. 2. Department of Microbiology, Nihon University School of Dentistry, Tokyo, Japan. 3. Department of Oral and Maxillofacial Surgery, Nihon University School of Dentistry, Tokyo, Japan. 4. Department of Periodontology, Nihon University School of Dentistry at Matsudo, Chiba, Japan. 5. Department of Endodontics, Nihon University School of Dentistry, Tokyo, Japan. 6. Department of Hematological Malignancy, Institute of Medical Science, Tokai University, Kanagawa, Japan. 7. Meikai University Research Institute of Odontology (M-RIO), Saitama, Japan. 8. Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. 9. Department of Microbiology, Nihon University School of Dentistry, Tokyo, Japan imai.kenichi@nihon-u.ac.jp.
Abstract
BACKGROUND/AIM: Human chronic periodontitis is a major health problem. Although some oral bacteria have been reported to be putative pathogens, Epstein-Barr virus (EBV) is reported to be associated with the progression of periodontitis. However, the role of EBV in the aetiology of periodontitis is unknown. Therefore, we investigated periodontal pathogenesis of EBV to confirm whether EBV-encoded latent membrane protein 1 (LMP1) induces Interleukin-8 (IL8) production in human gingival cells. MATERIALS AND METHODS: Real-time polymerase chain reaction, luciferase assay, enzyme-linked immunosorbent assay (ELISA), and western blotting were performed for determining IL8 mRNA expression, nuclear factor kappa B (NF-ĸB) transcription, IL8 production, and the phosphorylation of NF-ĸB p65 and Inhibitor of kappa B alpha (IĸBα), respectively, in Ca9-22 human gingival epithelial cells. Two LMP1 mutants lacking C-terminal activating region (CATR) domains responsible for activating NF-ĸB were used. RESULTS: Extremely high IL8 production was induced by LMP1 in time- and dose-dependent manner, where simultaneous phosphorylation of NF-κB p65 and IĸBα and transcription of NF-ĸB were observed. On the contrary, IL8 production and NF-ĸB transcription were drastically inhibited by dominant negative mutant of IĸBα. Moreover, the LMP1 mutants failed to induce IL8 production. CONCLUSION: Our findings suggest that due to CATR domains, LMP1 contributes to the progression of periodontitis via IL8 production attributable to NF-ĸB activation. Copyright
BACKGROUND/AIM: Humanchronic periodontitis is a major health problem. Although some oral bacteria have been reported to be putative pathogens, Epstein-Barr virus (EBV) is reported to be associated with the progression of periodontitis. However, the role of EBV in the aetiology of periodontitis is unknown. Therefore, we investigated periodontal pathogenesis of EBV to confirm whether EBV-encoded latent membrane protein 1 (LMP1) induces Interleukin-8 (IL8) production in human gingival cells. MATERIALS AND METHODS: Real-time polymerase chain reaction, luciferase assay, enzyme-linked immunosorbent assay (ELISA), and western blotting were performed for determining IL8 mRNA expression, nuclear factor kappa B (NF-ĸB) transcription, IL8 production, and the phosphorylation of NF-ĸB p65 and Inhibitor of kappa B alpha (IĸBα), respectively, in Ca9-22human gingival epithelial cells. Two LMP1 mutants lacking C-terminal activating region (CATR) domains responsible for activating NF-ĸB were used. RESULTS: Extremely high IL8 production was induced by LMP1 in time- and dose-dependent manner, where simultaneous phosphorylation of NF-κB p65 and IĸBα and transcription of NF-ĸB were observed. On the contrary, IL8 production and NF-ĸB transcription were drastically inhibited by dominant negative mutant of IĸBα. Moreover, the LMP1 mutants failed to induce IL8 production. CONCLUSION: Our findings suggest that due to CATR domains, LMP1 contributes to the progression of periodontitis via IL8 production attributable to NF-ĸB activation. Copyright
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