Human Periodontal Ligament Fibroblasts synthesize C-Reactive Protein and Th-Related Cytokines in response to Interleukin (IL)-6 trans-signaling

Abstract

Aim

To characterize the potential of human periodontal ligament fibroblasts (HPLF) to synthesize CRP and Th-related cytokines in response to IL-6 in periodontal health and apical inflammation.

Methodology

Primary HPLF stimulated with IL-6, soluble(s) IL-6 receptor (R) and controls were assayed for CRP, Th1, Th2, Th17 and Treg-related cytokines by quantitative real time PCR and ELISA, respectively. IL-6R mRNA expression and its soluble protein levels were screened in HPLF cultures, and ex vivo samples of healthy periodontal ligaments (n=5) and apical lesions (n=13). Data were analyzed with ANOVA or unpaired t-test.

Results

0.5 ng/mL IL-6 plus 1ng/mL of its soluble receptor (sIL-6R) for 24 h were effective in inducing CRP production. IL-6 alone had a mild dose-dependent effect; co-stimulation with sIL-6R significantly enhanced this effect, whereas it was completely abolished by the addition of IL-6R blocking antibody (p<0.05). Similarly, higher mRNA expression and protein levels of Th1, Th17 and partially Treg related cytokines were found for IL-6 combined with its soluble receptor versus the non-stimulated group and IL-6R antibody (p<0.05). IL-6R mRNA expression was slightly induced by IL-6 compared to THP-1 cells, but sILR-6 protein could not be detected in HPLF. High sIL-6R levels were detected in apical lesions and was immunolocalized to mononuclear inflammatory cells and proliferating epithelium.

Conclusions

IL-6 trans-signaling induced Th1 and Th17-related cytokines and represents an extra hepatic mechanism for PCR synthesis in human periodontal ligament fibroblasts, contributing to explain the bone destructive phenotype of apical lesions and eventually its systemic complications.

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