Salivary Biomarkers for Chronic Mucosal Inflammation

Objective: Under normal conditions, the healthy mucosa is protected by tightly regulated responses mediated through an array of pattern recognition receptors such as toll like receptors (TLRs). Specific TLRs recognize distinct pathogen associated molecular patterns (PAMPs) and mediate protection by constantly surveying their surroundings for potential threats and invasion. Recently soluble forms of TLR-2 and CD14, a co-receptor for TLR-4 have been identified in saliva. We hypothesized that changes in select salivary TLR may mediate altered microfloral epithelial interactions and contribute to the persistence and/or reoccurrence of the chronic mucosal lesions. The objective of this study was to investigate the salivary CD14, TLR-2 and TLR-4 levels in oral lichen planus (OLP) as the representative chronic oral mucosal inflammatory condition.

Method: We evaluated the levels of sCD14, TLR-2 and TLR-4 in unstimulated whole saliva by ELISA and immunoblot analysis. We measured the mRNA levels of these proteins in salivary epithelial cells by reverse transcriptase polymerase chain reaction. The presence of bacteria in/on oral epithelial cells was determined by Gram's staining.

Results: Our results suggest that while salivary sCD14 and sTLR-4 levels were upregulated in OLP, the sTLR-2 level was equivalent to that in normal controls. Interestingly, analysis of salivary epithelial cells showed that while CD14mRNA was upregulated, the TLR-2 mRNA was downregulated in OLP as compared to control. The TLR-4mRNA in salivary epithelial cells was equivalent in OLP and control. Furthermore, Gram's staining suggested that there were fewer bacteria per epithelial cell in the saliva of patients with OLP and BMS as compared to controls.

Conclusion: Since signaling via TLRs are known to mediate proinflammatory cytokine secretion, the observed alterations in the salivary CD14, TLR-2 and TLR-4 levels may represent a disturbance in the local immune response that contribute to the persistence of mucosal inflammation in OLP.