The immunopathogenic and immunomodulatory effects of interleukin-12 in periodontal disease.

Interleukin 12 (IL-12) is an inflammatory cytokine that promotes the response of the immune system. This cytokine has been implicated as a potent stimulator of several diseases characterized by inflammatory-induced bone destruction, such as rheumatoid arthritis and periodontitis. Yet, the exact role of IL-12 in the development and progress of periodontitis has not been clarified. Several studies have demonstrated a positive correlation between the level of IL-12 and the severity of periodontal destruction. Deletion of IL-12 in mice with periodontitis significantly suppressed the level of bone destruction. Interestingly, next to a role in modulating the pathogenesis, IL-12 also has immunological-regulatory properties. This cytokine induces expression of immunosuppressive molecules, such as indoleamine-pyrrole 2,3-dioxygenase (IDO). Thus, these findings suggest both negative and positive influences of IL-12 in periodontal disease. It is currently proposed that the diversity of action of cytokines is a molecular key which regulates biological development and homeostasis. Accordingly, the actions of IL-12 might be one of the mechanisms that regulate homeostasis of periodontal tissue during and following inflammation. Therefore, this article aims to review both destructive and protective functionalities of IL-12 with an emphasis on periodontal disease.

Interleukin-12 Induces Receptor Activator of Nuclear Factor-Kappa B Ligand Expression by Human Periodontal Ligament Cells.

BACKGROUND: Increased level of proinflammatory cytokine interleukin (IL)-12 correlates with the severity of periodontitis. Yet, a possible role of IL-12 in periodontal disease has not been clarified. The aim of this study is to investigate whether IL-12 affects expression of receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL), a potent osteoclast-stimulating factor, by human periodontal ligament (hPDL) cells. METHODS: To determine the effect of IL-12, hPDL cells were incubated with recombinant human IL-12 (p70) in a dose- (0 to 10 ng/mL) and time-dependent manner. Expression of RANKL was evaluated at mRNA and protein levels. Underlying signaling pathways of IL-12 were determined by using specific inhibitors. RESULTS: Under the influence of IL-12, hPDL cells expressed significantly higher levels of RANKL. Expression was mediated by signal transducer and activator of transcription 4 and NF-κB signaling pathways. Conditioned medium of IL-12-incubated cells proved to contain molecule(s) that induced RANKL expression. Addition of suramin (G protein-coupled receptor inhibitor) and ethylene glycol tetraacetic acid (calcium chelator) suggested existence of intermediate molecule(s) that could activate heterotrimeric G protein signaling in a calcium-dependent pathway. CONCLUSIONS: Expression of RANKL by hPDL cells significantly increased after IL-12 treatment. Therefore, this study supports a close interrelationship between immune and skeletal systems and suggests an osteolytic role of IL-12 in pathogenesis of periodontal disease.