Simvastatin inhibits the expression of inflammatory cytokines and cell adhesion molecules induced by LPS in human dental pulp cells

• Published in: International endodontic journal Vol. 50; no. 4; pp. 377 - 386
• Main Authors: Jung, J. Y., Woo, S. M., Kim, W. J., Lee, B. N., Nör, J. E., Min, K. S., Choi, C. H., Koh, J. T., Lee, K. J., Hwang, Y. C.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-04-2017
• Subjects: Blotting, Western; Cell adhesion & migration; Cell adhesion molecules; Cell Adhesion Molecules - metabolism; Cells, Cultured; Cytokines; Cytokines - metabolism; Cytoplasm; Dental pulp; Dental Pulp - cytology; Dental Pulp - drug effects; Dental Pulp - metabolism; Dentistry; Endodontics; Enzyme-Linked Immunosorbent Assay; Gene expression; Humans; Inflammation; inflammatory cytokines; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - metabolism; Interleukin 1; Interleukin 6; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; lipopolysaccharide; Lipopolysaccharides; Lipopolysaccharides - pharmacology; NF-kappa B - metabolism; NF-κB protein; NF‐κB; Nuclei; Phosphorylation; Polymerase chain reaction; Reverse Transcriptase Polymerase Chain Reaction; Simvastatin; Simvastatin - pharmacology; Statistical analysis; Transcription factors; Variance analysis; Vascular cell adhesion molecule 1; Vascular Cell Adhesion Molecule-1 - metabolism; simvastatin; NF-κB; cell adhesion molecules; inflammatory cytokines; lipopolysaccharide
• ISSN: 0143-2885; 1365-2591
• DOI: 10.1111/iej.12635

Aim
To investigate the effect of simvastatin on lipopolysaccharide (LPS)‐stimulated inflammatory cytokines, cell adhesion molecules and nuclear factor‐κB (NF‐κB) transcription factors in human dental pulp cells (HDPCs).
Methodology
The effect of LPS and simvastatin on human dental pulp cell (HDPCs) viability was measured using a 3‐[4, 5‐dimethylthiazol‐2‐yl]‐2, 5 diphenyltetrazolium bromide (MTT) assay. The expression of inflammatory cytokines and cell adhesion molecules was evaluated by reverse‐transcription polymerase chain reaction (RT‐PCR), enzyme‐linked immunosorbent assay (ELISA) and Western blot analysis. NF‐κB transcription factors were evaluated by Western blot analysis. Statistical analysis was performed with analysis of variance (anova).
Results
The viability of cells exposed to different concentrations of E. coli LPS, P. gingivalis LPS and simvastatin was not significantly different compared with that of control cells (P > 0.05). LPS significantly increased interleukin (IL)‐1β (P < 0.05) and IL‐6 mRNA expression (P < 0.05) and vascular cell adhesion molecule‐1 (VCAM‐1) (P < 0.05) and intercellular adhesion molecule‐1 (ICAM‐1) protein expression (P < 0.05) in HDPCs. Treatment with simvastatin significantly attenuated LPS‐stimulated production of IL‐1β, IL‐6, VCAM‐1 and ICAM‐1 (P < 0.05). Treatment with simvastatin decreased LPS‐induced expression of p65 and phosphorylation of IκB and also significantly decreased the phosphorylation of p65 and IκB in the cytoplasm and the level of p65 in the nucleus (P < 0.05).
Conclusions
Simvastatin has a suppressing effect on LPS‐induced inflammatory cytokine, cell adhesion molecules and NF‐κB transcription factors in HDPCs. Therefore, simvastatin might be a useful candidate as a pulp‐capping agent in vital pulp therapy.