B7-H1 and B7-DC receptors of oral squamous carcinoma cells are upregulated by Porphyromonas gingivalis

Immunobiology. 2011 Dec;216(12):1302-10. doi: 10.1016/j.imbio.2011.05.005. Epub 2011 Jun 12.

Abstract

The up-regulation of the B7-H1 receptors in host cells might influence the chronicity of inflammatory disorders that frequently precede the development of human cancers. B7-H1 expression has been detected in the majority of human cancers, leading to anergy and apoptosis of activated T cells, and enabling tumor cells to overcome host response. Porphyromonas gingivalis (P. gingivalis), a putative periodontal pathogen, is an etiologic agent of periodontitis and expresses a variety of virulence factors. In this study, the expression of B7-H1 and B7-DC receptors on squamous cell carcinoma cells SCC-25 and BHY and primary human gingival keratinocytes (PHGK) was analyzed after infection with two virulent P. gingivalis strains in vitro. After 48h, the cells were stained with antibodies for human B7-H1 and B7-DC and further analyzed by flow cytometry. RNA was extracted and gene expression of B7-H1 or B7-DC was quantified by real time PCR. After infection with P. gingivalis, both B7-H1 and B7-DC receptors were up-regulated. The mean fluorescence intensity (MFI) increased from 4.5 to 9.9 (B7-H1) and from 6.9 to 15.0 (B7-DC) (p<0.05, respectively) in SCC-25 cells. PHGK showed an increase from 4.8 to 12.4 (B7-H1) and from 5.5 to 15.6 (B7-DC) (p<0.05, respectively). Streptococcus salivarius K12, a commensal bacterium, caused no up-regulation. After 24h, the expression of B7H1 and B7-DC mRNA in infected cells, normalized to GAPDH and in relation to non-infected cells, was 6.4 fold (B7-H1) and 8.6 fold (B7-DC) higher. In PHGK B7-H1/DC mRNA expression increased 8.2 fold (B7-H1) and 5.9 fold (B7DC) (p<0.05) respectively. The results of the study demonstrate that in contrast to S. salivarius K12 virulent P. gingivalis strains are able to induce the expression of the B7-H1 and B7-DC receptors in squamous carcinoma cells and human gingival keratinocytes, which might facilitate immune evasion by oral cancers.

MeSH terms

  • Apoptosis / immunology
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / immunology
  • B7-H1 Antigen / metabolism*
  • Bacteroidaceae Infections / complications
  • Bacteroidaceae Infections / genetics
  • Bacteroidaceae Infections / immunology*
  • Bacteroidaceae Infections / pathology
  • Carcinoma, Squamous Cell / complications
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / immunology
  • Gingiva / pathology
  • Humans
  • Keratinocytes / immunology
  • Keratinocytes / metabolism*
  • Keratinocytes / microbiology
  • Keratinocytes / pathology
  • Porphyromonas gingivalis / immunology*
  • Porphyromonas gingivalis / pathogenicity
  • Programmed Cell Death 1 Ligand 2 Protein / genetics
  • Programmed Cell Death 1 Ligand 2 Protein / immunology
  • Programmed Cell Death 1 Ligand 2 Protein / metabolism*
  • T-Lymphocytes / pathology
  • Tumor Escape
  • Up-Regulation / immunology
  • Virulence

Substances

  • B7-H1 Antigen
  • Programmed Cell Death 1 Ligand 2 Protein