TY - JOUR
T1 - Rosuvastatin inhibits interleukin (IL)-8 and IL-6 production in human coronary artery endothelial cells stimulated with Aggregatibacter actinomycetemcomitans serotype b
AU - Gualtero, Diego F.
AU - Viafara-Garcia, Sergio M.
AU - Morantes, Sandra J.
AU - Buitrago, Diana M.
AU - Gonzalez, Octavio A.
AU - Lafaurie, Gloria I.
N1 - Publisher Copyright:
© 2017 American Academy of Periodontology. All rights reserved.
PY - 2017/2
Y1 - 2017/2
N2 - Background: Rosuvastatin exhibits anti-inflammatory effects and reduces periodontal diseases and atherosclerosis; however, its role in regulating periodontopathogen-induced endothelial proinflammatory responses remains unclear. The purpose of this study is to determine whether rosuvastatin can reduce the proinflammatory response induced by Aggregatibacter actinomycetemcomitans (Aa) in human coronary artery endothelial cells (HCAECs). Methods: HCAECs were stimulated with purified Aa serotype b lipopolysaccharide (LPS) (Aa-LPS), heat-killed (HK) bacteria (Aa-HK), or live bacteria. Expression of Toll-like receptors and cellular adhesion molecules were evaluated by fluorometric enzyme-linked immunosorbent assay. Endothelial cell activation was evaluated by quantifying nuclear factor (NF)-kappa B-p65 and cytokine expression levels by quantitative polymerase chain reaction and flow cytometry. Effect of rosuvastatin in expression of the atheroprotective factor Krüppel-like factor 2 (KLF2) and cytokines were also studied using similar approaches. Results: HCAECs showed increased interleukin (IL)-6, IL-8, intercellular adhesion molecule 1, and platelet endothelial cell adhesion molecule 1 expression when stimulated with Aa-LPS or Aa-HK. NF-κB-p65 activation was induced by all antigens. Aa-induced IL-6 and IL-8 production was inhibited by rosuvastatin, particularly at higher doses. Interestingly, reduced IL-6 and IL-8 levels were observed in HCAECs stimulated with Aa in the presence of higher concentrations of rosuvastatin. This anti-inflammatory effect correlated with a significant increase of rosuvastatin-induced KLF2. Conclusions: These results suggest Aa-induced proinflammatory endothelial responses are regulated by rosuvastatin in a mechanism that appears to involve KLF2 activation. Use of rosuvastatin to prevent cardiovascular disease may reduce risk of endothelial activation by bacterial antigens.
AB - Background: Rosuvastatin exhibits anti-inflammatory effects and reduces periodontal diseases and atherosclerosis; however, its role in regulating periodontopathogen-induced endothelial proinflammatory responses remains unclear. The purpose of this study is to determine whether rosuvastatin can reduce the proinflammatory response induced by Aggregatibacter actinomycetemcomitans (Aa) in human coronary artery endothelial cells (HCAECs). Methods: HCAECs were stimulated with purified Aa serotype b lipopolysaccharide (LPS) (Aa-LPS), heat-killed (HK) bacteria (Aa-HK), or live bacteria. Expression of Toll-like receptors and cellular adhesion molecules were evaluated by fluorometric enzyme-linked immunosorbent assay. Endothelial cell activation was evaluated by quantifying nuclear factor (NF)-kappa B-p65 and cytokine expression levels by quantitative polymerase chain reaction and flow cytometry. Effect of rosuvastatin in expression of the atheroprotective factor Krüppel-like factor 2 (KLF2) and cytokines were also studied using similar approaches. Results: HCAECs showed increased interleukin (IL)-6, IL-8, intercellular adhesion molecule 1, and platelet endothelial cell adhesion molecule 1 expression when stimulated with Aa-LPS or Aa-HK. NF-κB-p65 activation was induced by all antigens. Aa-induced IL-6 and IL-8 production was inhibited by rosuvastatin, particularly at higher doses. Interestingly, reduced IL-6 and IL-8 levels were observed in HCAECs stimulated with Aa in the presence of higher concentrations of rosuvastatin. This anti-inflammatory effect correlated with a significant increase of rosuvastatin-induced KLF2. Conclusions: These results suggest Aa-induced proinflammatory endothelial responses are regulated by rosuvastatin in a mechanism that appears to involve KLF2 activation. Use of rosuvastatin to prevent cardiovascular disease may reduce risk of endothelial activation by bacterial antigens.
KW - Atherosclerosis
KW - Immunity, Innate
KW - KLF2 proteins
KW - Lipopolysaccharides
KW - Periodontitis
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UR - http://www.scopus.com/inward/citedby.url?scp=85011945248&partnerID=8YFLogxK
U2 - 10.1902/jop.2016.160288
DO - 10.1902/jop.2016.160288
M3 - Article
C2 - 27739345
AN - SCOPUS:85011945248
SN - 0022-3492
VL - 88
SP - 225
EP - 235
JO - Journal of Periodontology
JF - Journal of Periodontology
IS - 2
ER -
