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

• Published in: Immunobiology (1979) 2011-12, Vol.216 (12), p.1302-1310
• Main Authors: Groeger, Sabine, Domann, Eugen, Gonzales, Jose R, Chakraborty, Trinad, Meyle, Joerg
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Allergy and Immunology; Apoptosis - immunology; B7-H1; 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; Death receptor; Gene Expression Regulation, Neoplastic - immunology; Gingiva - pathology; Humans; Keratinocytes - immunology; Keratinocytes - metabolism; Keratinocytes - microbiology; Keratinocytes - pathology; Porphyromonas gingivalis; 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; Squamous carcinoma cells; Streptococcus salivarius; T-Lymphocytes - pathology; Tumor Escape; Up-Regulation - immunology; Upregulation; Virulence
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2011.05.005

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 48 h, 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 24 h, 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. salivariu s 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.