LPS Responsiveness in Periodontal Ligament Cells is Regulated by Tumor Necrosis Factor-α

Abstract

Gingival fibroblasts function as accessory immune cells and are capable of synthesizing cytokines in response to lipopolysaccharides (LPS) from Gram-negative microbes. Recently, we have isolated, cloned, and characterized two cell lines which exhibit characteristics of periodontal ligament (PDL) cells. In this report, we demonstrate that PDL cells showing osteoblast-like phenotype are not LPS-responsive cells. However, treatment of PDL cells with tumor necrosis factor-alpha (TNF-alpha) inhibits the expression of their osteoblast-like characteristics. As a consequence of this TNF-alpha-induced phenotypic change, PDL cells become LPS-responsive, i.e., synthesize several pro-inflammatory cytokines in response to LPS. These phenotypic changes occur at concentrations of TNF-alpha that are frequently observed in tissue exudates during periodontal inflammation, suggesting a physiological significance for these in vitro observations. It is of interest that TNF-alpha-induced phenotypic changes in PDL cells are transient, since removal of rhTNF-alpha from the supernatants of PDL cell cultures results in re-acquisition of the osteoblast-like characteristics and lack of LPS responsiveness of PDL cells. These results suggest that TNF-alpha, by regulating the PDL cell functions, may allow these cells to participate in the disease process as accessory immune cells at the expense of their structural properties.

Viability, adhesion, and bone phenotype of osteoblast‐like cells on polyelectrolyte multilayer films

“…42,43 TNF-␣ production, for example, is often a real problem during implant integration because this proinflammatory cytokine induces the secretion of other ones while it downregulates osteoblast phenotype expression. 33 Moreover, TNF-␣ activates osteoclasts and triggers bone resorption. 42 The fact that none of our polyelectrolyte multilayer constructions induced TNF-␣ production constitutes a very positive feature.…”

“…31 However, for PDL cells, osteoblast phenotype expression can easily be downregulated. This can happen, for example, in the case of inflammation of periodontal tissue, when proinflammatory cytokines, 32,33 various growth factors, 34 or both are produced. In this case, PDL cells temporarily fail to express osteoblast markers.…”

Is Fibroblast Heterogeneity Relevant To the Health, Diseases, and Treatments of Periodontal Tissues?

“…In vivo, fibroblasts exhibit a range of morphological and functional characteristics, including a cigar-shaped or stellate morphology in vitro but a highly variable set of morphologies in vivo (Fig I) These cells have the ability to synthesize various extracellular proteins such as collagen and fibronectin but can also undertake other functions (e.g., as immune accessory cells; Agarwal et al, 1995;Quintero et al, 1995;Fig. 2) which extend their utility as "architects and caretakers of connective tissues". At the outset, it is worth noting that the gingival and periodontal ligament connective tissues contain many different types of cells, of which the fibroblast is the most numerous (Schroeder et al, 1973) Thus, it is possible to describe heterogeneous behavior in gingival or periodontal ligament cell populations that are in fact the result of a description of totally different cell types.…”

Periodontal Ligament Stem Cells

“…One of the components of the cell wall of gram-negative anaerobic bacteria, lipopolysaccharide, which is a complex glycolipid (Lamont et al, 1998), promotes the expression of pro-inflammatory cytokines, such as interleukin-1 beta and tumor necrosis factor-alpha, in macrophages and PDL cells (Lindemann et al, 1988;Wada et al, 2004). These cytokines are reported not only to disturb the function of PDL cells (Quintero et al, 1995;Agarwal et al, 1998), but also to stimulate the production of matrix metalloproteases (MMPs), such as MMP-1, in PDL cells (Oyama et al, 2007;Xiang et al, 2009). MMP-1 is the major proteolytic enzyme that can cleave native type I and type III collagens, suggesting its aggressive contribution to the destruction of the PDL structure (Birkedal-Hansen, 1993).…”