Differential Gene Expression of Inflammatory Signaling in Localized Aggressive Periodontitis
Weiner, Whitney D.
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Objective: To determine if expression of innate immune response genes differs between localized aggressive periodontitis (LAP) patients and periodontally healthy matched controls. Materials and Methods: A comprehensive literature review of all genes reported to have a role in AP identified 38 genes. STRING database (version 9.0) analysis indicated 34 of the 38 genes were involved in innate immunity. Based on functional analyses, 20 candidate genes were selected to test our hypothesis that differential expression of innate immune response genes to inflammatory stimuli in the gingival epithelium could underlie LAP susceptibility. Gingival biopsies were obtained from 3 AP patients and 3 controls (African American females age 15-21). Primary gingival keratinocytes were isolated, cultured, and incubated. Cells were treated with human recombinant interleukin (IL)-1β, Porphyromonas gingivalis LPS (PgLPS), Aggregatibacter actinomycetemcomitans (AaLPS), or medium only to evaluate gene expression at 0, 3 and 6 hours. RNA was isolated and differential gene expression was analyzed using QuantiGene 2.0 Multiplex Assays. Results: At baseline, there were no differences in gene expression in patients versus controls. Stimulation with IL-1β elicited main effect of disease status for NLRP3 (p=0.047) and CCL2 (p=0.045). Following all 3 treatments (AaLPS, PgLPS, and IL-1β), epithelial cells from AP subjects were found to have higher gene expression for NLRP3 and lower gene expression for CCL2 than controls. Overall, LY96 and NLRP3 gene expression was higher (p=0.016 and p=0.005, respectively), while CCL2 gene expression was lower (p<0.0001), across all treatment conditions and both time points (3 and 6 hours) in AP patients. Conclusion: The inflammatory triggers of AaLPS, PgLPS, and IL-1β elicited differential expression for several genes involved in innate immunity. These findings offer insight to host immune responses involved in LAP pathogenesis and are consistent with a dysregulation of inflammatory signaling following immune challenge in LAP patients. Clinical significance: Identification of genes that are differentially expressed in response to infectious stimuli in AP patients may enable better understanding of disease etiology, nosology, and identification of treatment targets.