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  • Title: Differential regulation of innate immune response genes in gingival epithelial cells stimulated with Aggregatibacter actinomycetemcomitans.
    Author: Laube DM, Dongari-Bagtzoglou A, Kashleva H, Eskdale J, Gallagher G, Diamond G.
    Journal: J Periodontal Res; 2008 Feb; 43(1):116-23. PubMed ID: 18004991.
    Abstract:
    BACKGROUND AND OBJECTIVE: The gingival epithelium provides the first line of defense against colonization by periodontal pathogens, both as a physical barrier and by the production of inducible innate immune mediators such as beta-defensins and pro-inflammatory cytokines. The gram-negative bacterium Aggregatibacter actinomycetemcomitans is implicated in the pathogenesis of localized aggressive periodontitis, although the bacterium is found widely in the healthy population. We hypothesized that gingival epithelial cell-derived innate immune mediators triggered in response to A. actinomycetemcomitans infection may play an important role in increased susceptibility to infection. MATERIAL AND METHODS: Primary cultures of human gingival epithelial cells were cultured in the presence of A. actinomycetemcomitans. Total mRNA was examined for the presence of innate immune markers using RT-PCR. RESULTS: We show here that the mRNA levels of human beta-defensin 2 and interleukin-8 are elevated by live cultures of a clinical isolate of A. actinomycetemcomitans in cultured gingival epithelial cells from healthy individuals, but not by A. actinomycetemcomitans lipopolysaccharide. Cells from a patient with localized aggressive periodontitis, however, did not respond to this bacterial stimulation. In contrast, the pro-inflammatory cytokine interleukin-19 was induced in cells from both localized aggressive periodontitis and healthy subjects. Examination of Toll-like receptors and associated adapter molecules indicated lower levels of Toll-like receptor 2 mRNA in the localized aggressive periodontitis patient-derived cells compared with cells from healthy subjects. CONCLUSION: These results suggest that a differential expression of innate immune response genes to A. actinomycetemcomitans in the gingival epithelium could be an underlying factor of susceptibility to localized aggressive periodontitis.
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