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

Benjar Issaranggun Na Ayuthaya, Vincent Everts, Prasit Pavasant

J Periodontol. 2017 Jul;88(7):e109-e119.

PMID: 28398106

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR4248603 Interleukin-12 human Interleukin-12 human Price
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