Differential profiles of soluble and cellular toll like receptor (TLR)-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 large groups of microorganisms. The oral epithelial cells respond to most periodontopathic bacteria via TLR-2 and TLR-4. 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. Many studies have previously reported the presence of elevated numbers of viable exfoliated epithelial cells in the saliva of patients with chronic periodontitis. The objective of this study was to investigate the potential value of salivary sTLR-2 and sTLR-4 together with 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 with either periodontitis or gingivitis. The sTLR-2 and sTLR4 in saliva was measured by enzyme-linked immunosorbent assay. The TLR-2 and TLR-4 transcript in the epithelial cells in saliva was measured 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 the sTLR-2 and the paired epithelial cell associated TLR-2 mRNA exhibited a direct correlation (r2 = 0.62), that of sTLR4 and 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 the epithelial cells could provide clinically relevant markers of disease progression from gingivitis to periodontitis.

Oral epithelial expression of angiotensin converting enzyme-2: Implications for COVID-19 diagnosis and prognosis

“…Epithelia are the primary barrier to microbial infection transmitted by contact with the exposed environment. As such, the epithelial cells express cell surface receptors that allow attachment to and penetration of the cell membrane by the microbes 20,22 . The distribution and density of the attachment receptors have been shown to be related with the degree of differentiation of the epithelia.…”

“…Isolation of epithelial cells in saliva: Unstimulated whole saliva was collected by the drooling method for 5-10 minutes into a 15ml chilled centrifuge tube after obtaining informed consent as described 20,21 . All samples were centrifuged at 250g for 10 minutes at 4C.…”

Involvement of Cathepsins in Innate and Adaptive Immune Responses in Periodontitis

“…M2 macrophages have been shown to play a role in relief of inflammation and thus have decreased capacity to produce cytokines. Macrophages express high levels of TLR2 and TLR4 [26], which shift to the M1 phenotype in gingival tissues of patients with chronic periodontitis [27]. Interestingly, M1 macrophages can transform into M2 macrophages by exosomes derived from gingival mesenchymal stem cells, which is beneficial for suppressing the immune responses [28].…”

Salivary Biomarkers of Chronic Periodontitis

“…24,25 Salivary nitric oxide (NO) metabolite and toll-like receptors (TLR-2 and TLR-4) are used as biomarkers which are predictive indicator of periodontal inflammatory condition. 26,27 Protein carbonyl (PO) causes oxidative damage may leads to decline of protein function. Higher levels of PO and salivary cortisol present in Chronic periodontitis are used as salivary biomarkers.…”