IADR Abstract Archives
Role of IFI16 in the Pathogenesis of Periodontitis
Objectives: Our previous GWAS study found interferon, gamma-inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) SNPs associated with higher levels of periodontal microorganisms and increased extent of periodontal disease, suggesting the need for further functional studies. The purpose of this study was to evaluate whether IFI16 is induced in murine experimental periodontitis and whether it modulates the innate immune response via AIM2.
Methods: Endothelial cells (HUVEC) treated with live periodontal bacteria Aa or Fn were evaluated for IFI16 and AIM2 expression by Western blot . Cells overexpressing IFI16 (pCMV-HA-IFI16) were treated with periodontal pathogens Aa, Pg or Fn and evaluated for chemokine expression. Ligature-induced periodontitis was evaluated for tissue expression of Ifi204 (murine homologous IFI16) and AIM2 by (qRT-PCR) in C57BL/6 WT mice (n=10). Alveolar bone loss (ABC-CEJ distance) was measured by microCT analysis in Ifi204-/- and WT controls induced for periodontitis. Testing for significant differences was done by ANOVA and t-test (p≤0.05)
Results: Periodontal bacteria Fn and Aa induced a slight increase in IFI16 expression compared to control (1.3-1.4 times ). pCMV-HA-IFI16 overexpressed cells showed significant decreases in CCL2, CCL3 and CCL4 chemokine responses upon periodontal pathogen stimulation compared to controls (p≤0.05). Gingival samples from ligature-induced WT mice showed significant increases in expression of Ifi204 (2.4-fold) and AIM2 (2.8-fold) as compared to healthy controls (p≤0.05). After 10-day ligature induced periodontitis, Ifi204-/- mice showed a significantly higher mean bone loss compared to WT mice [0.42mm (SD=0.092mm) vs. 0.34mm (SD=0.083mm), p≤ 0.05].
Conclusions: Our data shows that IFI16/Ifi204 expression is increased in the ligature-induced periodontitis model, and KO mice show greater bone loss. The observation that IFI16 overexpression in cell lines suppresses the chemokine response supports the role of IFI16 as a modulator of the host response to periodontal microorganisms.
Methods: Endothelial cells (HUVEC) treated with live periodontal bacteria Aa or Fn were evaluated for IFI16 and AIM2 expression by Western blot . Cells overexpressing IFI16 (pCMV-HA-IFI16) were treated with periodontal pathogens Aa, Pg or Fn and evaluated for chemokine expression. Ligature-induced periodontitis was evaluated for tissue expression of Ifi204 (murine homologous IFI16) and AIM2 by (qRT-PCR) in C57BL/6 WT mice (n=10). Alveolar bone loss (ABC-CEJ distance) was measured by microCT analysis in Ifi204-/- and WT controls induced for periodontitis. Testing for significant differences was done by ANOVA and t-test (p≤0.05)
Results: Periodontal bacteria Fn and Aa induced a slight increase in IFI16 expression compared to control (1.3-1.4 times ). pCMV-HA-IFI16 overexpressed cells showed significant decreases in CCL2, CCL3 and CCL4 chemokine responses upon periodontal pathogen stimulation compared to controls (p≤0.05). Gingival samples from ligature-induced WT mice showed significant increases in expression of Ifi204 (2.4-fold) and AIM2 (2.8-fold) as compared to healthy controls (p≤0.05). After 10-day ligature induced periodontitis, Ifi204-/- mice showed a significantly higher mean bone loss compared to WT mice [0.42mm (SD=0.092mm) vs. 0.34mm (SD=0.083mm), p≤ 0.05].
Conclusions: Our data shows that IFI16/Ifi204 expression is increased in the ligature-induced periodontitis model, and KO mice show greater bone loss. The observation that IFI16 overexpression in cell lines suppresses the chemokine response supports the role of IFI16 as a modulator of the host response to periodontal microorganisms.