Differential regulation of innate immune response genes in gingival epithelial cells stimulated with Aggregatibacter actinomycetemcomitans.
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.


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.


CONCLUSIONS
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.
Laube
D M
DM
Department of Oral Biology, UMDNJ-New Jersey Dental School, Newark, NJ 07103, USA.
Dongari-Bagtzoglou
A
A
Kashleva
H
H
Eskdale
J
J
Gallagher
G
G
Diamond
G
G
D018929:Cell Culture Techniques; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D005802:Genes, MHC Class II / Q000276:immunology*; D005881:Gingiva / Q000166:cytology* / Q000276:immunology / Q000382:microbiology; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis; D015661:Pasteurellaceae / Q000276:immunology*; D010518:Periodontitis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D023083:beta-Defensins / Q000032:analysis
D016209:Interleukin-8; D023083:beta-Defensins