Mechanisms involved in regulation of periodontal ligament cell production of pro-inflammatory cytokines: Implications in periodontitis

Abstract

It is well recognized that human periodontal ligament cells (PDL cells) may represent local immune cells of the periodontal tissues. However, it is unclear whether they represent "true" immune cells, since they can produce pro-inflammatory cytokines not only after stimulation with bacterial lipopolysaccharides but also in response to other stimuli such as mechanical stress. Stimulation with bacterial lipopolysaccharides strongly enhances PDL cell production of pro-inflammatory cytokines through activation of toll-like receptors and NF-κB signaling. Less information is available regarding putative modulators of cytokine production and their mechanisms of action in PDL cells. The anti-inflammatory glucocorticoid dexamethasone reduces lipopolysaccharide-induced PDL cell production of cytokines. Recent observations show that vitamin D and the antimicrobial peptide LL-37 antagonize lipopolysaccharide-stimulated PDL cell production of pro-inflammatory cytokines. Secretory leukocyte protease inhibitor is endogenously expressed by PDL cells, and this protein negatively regulates PDL cell-evoked cytokine production. More information and knowledge about the regulation of PDL cell production of cytokines may clarify the role of PDL cells in oral innate immunity and their importance in periodontitis.

Keywords: NF-κB; inflammation; innate immunity; periodontitis.

Figure 1

Modulation of LPS‐induced pro‐inflammatory cytokine production in human PDL cells. Vitamin D/VDR presumably attenuates cytokine production at the transcriptional level. The antimicrobial peptide LL‐37 can bind and neutralize LPS extracellularly, but it may also interact with the synthesis of cytokines downstream of NF‐κB, leading to reduced cellular cytokine production. Secretory leukocyte protease inhibitor (SLPI) is a protein expressed in PDL cells, and it seems to act as a negative regulator of cytokine production via interaction with TLR4 expression and NF‐κB activity. Glucocorticoids (GC) reduce PDL cell production of pro‐inflammatory cytokines probably through inhibition of NF‐κB activity. Please, note that TLR4 is a plasma membrane receptor