Differential Profiles of Soluble and Cellular Toll-like Receptors (TLRs) 2 and 4 in Chronic Periodontitis.

Abstract

Chronic periodontitis is a common inflammatory disease initiated by a complex microbial biofilm and mediated by the host response causing destruction of the supporting tissues of the teeth. Host recognition of pathogens is mediated by toll-like receptors (TLRs) that bind conserved molecular patterns shared by groups of microorganisms. The oral epithelial cells respond to most periodontopathic bacteria via TLR-2 and TLR-4. Many studies have previously reported the presence of elevated numbers of viable exfoliated epithelial cells (SEC) in the saliva of patients with chronic periodontitis. In addition to the membrane-associated receptors, soluble forms of TLR-2 (sTLR-2) and TLR-4 (sTLR-4) have been identified and are thought to play a regulatory role by binding microbial ligands. sTLR-2 has been shown to arise from ectodomain shedding of the extracellular domain of the membrane receptor and sTLR-4 is thought to be an alternate spliced form. The objective of this study was to investigate the potential value of salivary sTLR-2/4 and the paired epithelial cell-associated TLR-2/4 mRNA as diagnostic markers for chronic periodontitis. Unstimulated whole saliva was collected after obtaining informed consent from 40 individuals in either periodontitis or gingivitis cohorts. The levels of sTLR-2/4 were measured by enzyme-linked immunosorbent assay (ELISA). SEC TLR-2/4 transcripts were quantitated by real time polymerase chain reaction. While levels of sTLR-2 exhibited an inverse correlation, sTLR-4 positively correlated with clinical parameters in the gingivitis cohort. Interestingly, both correlations were lost in the periodontitis cohort indicating a dysregulated host response. On the other hand, while sTLR-2 and the paired SEC associated TLR-2 mRNA exhibited a direct correlation (r2=0.62), that of sTLR4 and SEC TLR-4 mRNA exhibited an inverse correlation (r2=0.53) in the periodontitis cohort. Collectively, assessments of salivary sTLR2 and sTLR4 together with the respective transcripts in SECs could provide clinically relevant markers of disease progression from gingivitis to periodontitis.