EBV LMP1 in Gingival Epithelium Potentially Contributes to Human Chronic Periodontitis via Inducible IL8 Production

In Vivo. 2019 Nov-Dec;33(6):1793-1800. doi: 10.21873/invivo.11670.

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.

Keywords: EBV; IL8; LMP1; NF-ĸB; gingival epithelial cells; periodontitis.

MeSH terms

  • Cell Line
  • Chronic Periodontitis / metabolism*
  • Epithelial Cells / metabolism*
  • Epithelial Cells / virology
  • Epithelium / metabolism*
  • Epithelium / virology
  • Gingiva / metabolism*
  • Gingiva / virology
  • Herpesvirus 4, Human / metabolism*
  • Humans
  • Interleukin-8 / metabolism*
  • NF-kappa B / metabolism
  • Signal Transduction / physiology
  • Transcription Factor RelA / metabolism
  • Viral Matrix Proteins / metabolism*

Substances

  • CXCL8 protein, human
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Interleukin-8
  • NF-kappa B
  • Transcription Factor RelA
  • Viral Matrix Proteins