Immunohistochemical localization of Toll‐like receptors 2 and 4 in gingival tissue from patients with periodontitis

Abstract

The present study investigated the expression of Toll‐like receptor (TLR) 2, TLR4, cluster of differentiation (CD) 14 and CD1a in human periodontitis gingiva using immunohistochemical methods. The specimens were classified according to the degree of inflammation into three groups (mild, moderate and severe). We established three zones in which to evaluate the ratios of TLR2‐, TLR4‐, CD14‐ and CD1a‐positive cells to total cells in the connective tissues of each section. TLR2 and TLR4 were expressed in human periodontal tissues, and the ratio of TLR2‐positive cells was highest overall in zone 1 (connective tissue subjacent to pocket epithelium) of the severe group and that of TLR4‐positive cells was higher in the severe group than in the other groups. These results suggest that TLR2 and TLR4 participate in the innate immune response to stimulation by bacterial products in periodontal tissues. The ratio of CD14‐positive cells was lowest overall in zone 1 of the severe group and that of CD1a was higher in the severe group than in the other groups. These results suggest that CD14 may be down‐regulated during the development of inflammation and/or dendritic cells might infiltrate chronically inflamed gingival tissue.

Oral Mucosal Endotoxin Tolerance Induction in Chronic Periodontitis

“…MC and m express TLRs constitutively (2), are found in the gingival tissues (31), and express TLRs in situ (Fig. 2) (28). We therefore used peripheral blood-derived MC as an in vitro model of TLR expression to determine if TLRs could be differentially regulated by their agonists (30).…”

“…TLR2, along with TLR1/ 6, recognizes gram-positive peptodoglycans (e.g., from oral commensals) (36). One recent study indicates that both TLR2-and TLR4-positive cells infiltrate the oral mucosa (i.e., gingiva) in periodontal health and disease (28), but very little is understood about the overall expression patterns of PRRs in the human oral mucosa in health and in chronic periodontitis (CP) and how they regulate local immune responsiveness. While monocytes (MC)/macrophages (m) constitutively express TLRs, recent evidence indicates that TLR expression can be downregulated by repeated exposure to LPS, resulting in downmodulation of the inflammatory cytokine response (i.e., endotoxin tolerance) (11).…”

MAP Kinase Phosphatase-1 Protects against Inflammatory Bone Loss

“…LPS can stimulate the expression of IL-1ß, TNF-α, IL-6, and RANKL by activating the innate immune response (Nakashima et al, 2000;Jiang et al, 2002;Kikuchi et al, 2003). Within periodontal tissues, TLR-2 and -4 expression is increased in severe disease states, suggesting that these receptors have an increased capacity to signal and influence downstream cytokine expression (Mori et al, 2003). TLR-4 signaling activates MyD88-dependent pathways to subsequent activation of IRAK, TRAF6, and, ultimately, nuclear factor kappa B (NF-κB), which is required for cytokine induction.…”

The Role of TLRs in the Pathogenesis of Periodontal Diseases

“…An abundance of TLR2-positive cells has been observed also in connective tissue subjacent to the pocket epithelium [28]. Gingival epithelial cells express TLR3 and TLR9 [26] and human gingival fibroblasts express TLR2, TLR4 and TLR9 [29,30].…”

“…Subgingival plaque from diseased sites strongly activated TLR4, while matched plaque samples obtained from healthy sites were significantly more variable with some samples displaying strong TLR4 antagonism while others were strong TLR4 agonists when combined with F. nucleatumLPS [38].Wang et al found increased expression of TLR-2 in human gingival fibroblasts of inflammatory gingiva than those in healthy group [39]. Mori et al investigated the expression of TLR2 and TLR4 in human periodontal disease and showed higher TLR2 positive cells in mild group and higher TLR4 positive cells in severe gingivitis [40]. …”