title: Simvastatin inhibits the expression of inflammatory cytokines and cell adhesion molecules induced by LPS in human dental pulp cells.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
authors.affiliation: Department of Physiology, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Jung
authors.affiliation: Department of Physiology, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, Korea.
authors.forename: S M
authors.initials: SM
authors.lastname: Woo
authors.affiliation: Department of Physiology, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, Korea.|Research Center for Biomineralization Disorders, Chonnam National University, Gwangju, Korea.
authors.forename: W J
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Conservative Dentistry, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, Korea.
authors.forename: B N
authors.initials: BN
authors.lastname: Lee
authors.affiliation: Angiogenesis Research Laboratory, Department of Cariology, Restorative Sciences, Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Nör
authors.affiliation: Department of Conservative Dentistry, School of Dentistry, Chonbuk National University, Jeonju, Korea.
authors.forename: K S
authors.identifier: http://orcid.org/0000-0002-1928-3384
authors.initials: KS
authors.lastname: Min
authors.affiliation: Department of Preventive and Public Health Dentistry, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, Korea.
authors.forename: C H
authors.initials: CH
authors.lastname: Choi
authors.affiliation: Research Center for Biomineralization Disorders, Chonnam National University, Gwangju, Korea.
authors.forename: J T
authors.initials: JT
authors.lastname: Koh
authors.affiliation: Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: K J
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Research Center for Biomineralization Disorders, Chonnam National University, Gwangju, Korea.|Department of Conservative Dentistry, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, Korea.
authors.forename: Y C
authors.initials: YC
authors.lastname: Hwang
mesh_terms: D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019821:Simvastatin / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019821:Simvastatin
keywords: NF-κB; cell adhesion molecules; inflammatory cytokines; lipopolysaccharide; simvastatin