Toll-like receptors 1/2/4/6 and nucleotide-binding oligomerization domain-like receptor 2 are key damage-associated molecular patterns sensors on periodontal resident cells

Abstract

Background: Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are innate, damage-associated molecular patterns (DAMP) sensors. Their expressions in human periodontal resident cells and reactions toward irritations, such as hypoxia and lipopolysaccharide (LPS), remain not well characterized. This cross-sectional study aimed to investigate and characterize TLRs, NOD1/2 and NLRP1/2 expressions at the dento-gingival junction. Methods: Immunohistochemistry screening was carried out on periodontal tissue biopsies sections, while selected DAMP sensors signal and protein expression under Escherichia coli LPS (2 µg/mL) and/or hypoxia (1% O2), 24 h, by human gingival keratinocytes (HGK) or fibroblasts (HGF) were investigated. Results: Positive TLR1/2/4/5/6, NOD1/2 and NLRP1/2 immunostaining were observed in healthy and periodontitis biopsies with apparently more pocket epithelial cells positive for TLR2, TLR4 and NOD1/2. TLR1-6, NOD1/2 and NLRP1/2 messengers were detected in gingival/periodontal biopsies as well as healthy HGK and HGF explants. LPS and/or hypoxia induced signals and protein upregulation of NOD2 in HGKs or TLR1/6 and NOD2 in HGFs. Conclusion: Transcripts and proteins of TLR1/2/4/5/6, NOD1/2 and NLRP1/2 were expressed in human periodontal tissue in health and disease. Putting all observations together, NOD2, perhaps with TLR1/2/4/6, might be considered key, damage-associated molecular pattern sensors on periodontal resident cells.