Intracellular Adhesion Molecule‐1 Is Regulated by Porphyromonas gingivalis Through Nucleotide Binding Oligomerization Domain‐Containing Proteins 1 and 2 Molecules in Periodontal Fibroblasts

Abstract

The mechanism by which Porphyromonas gingivalis regulates intracellular adhesion molecule 1 (ICAM-1) expression in human periodontal ligament cells (hPDLCs) and human gingival fibroblasts (hGFs) is unknown. The aim of this study is to investigate whether nucleotide binding oligomerization domain-containing protein (NOD) 1 and NOD2 are involved in this process and the clinical significance of ICAM-1 in periodontitis. hPDLCs and hGFs were treated with P. gingivalis, l-Ala-γ-d-glutamyl-mesodiaminopimelic acid (an agonist for NOD1), and muramyl dipeptide (an agonist for NOD2). Alternatively, cells transfected with small interfering RNA targeting NOD1and NOD2 were treated with P. gingivalis. ICAM-1, NOD1, and NOD2 were detected at mRNA and protein levels. In addition, clinical examinations were performed in 30 healthy controls and 40 patients with chronic periodontitis (CP) before and after treatment, and serum-soluble ICAM-1 (sICAM-1) levels in these individuals were detected by enzyme-linked immunosorbent assay. This study shows that P. gingivalis caused an increase in ICAM-1, NOD1, and NOD2 expression in periodontal fibroblasts. There was a linear correlation between ICAM-1 and NOD1 and NOD2 levels. Activation of NOD1 and NOD2 by the specific agonist led to the upregulation of ICAM-1, whereas knocking down NOD1 and NOD2 caused a reduction in P. gingivalis-induced ICAM-1 production. Furthermore, sICAM-1 levels were higher in patients with CP than in healthy controls and were positively related to the clinical periodontal parameters. After periodontal treatment, sICAM-1 levels decreased significantly. The present results indicate that sICAM-1 levels are correlated to the severity of periodontitis. NOD1 and NOD2 mediate P. gingivalis-induced ICAM-1 production in periodontal fibroblasts. NOD1 and NOD2 could be considered potential targets for periodontal therapy.