Exp Mol Med.  2014 Oct;46(10):e118. 10.1038/emm.2014.65.

Chronic stress enhances progression of periodontitis via alpha1-adrenergic signaling: a potential target for periodontal disease therapy

• Lu H
• Xu M
• Wang F
• Liu S
• Gu J
• Lin S

• KMID: 2155383
• DOI: http://doi.org/10.1038/emm.2014.65

Abstract

This study assessed the roles of chronic stress (CS) in the stimulation of the sympathetic nervous system and explored the underlying mechanisms of periodontitis. Using an animal model of periodontitis and CS, the expression of tyrosine hydroxylase (TH) and the protein levels of the alpha1-adrenergic receptor (alpha1-AR) and beta2-adrenergic receptor (beta2-AR) were assessed. Furthermore, human periodontal ligament fibroblasts (HPDLFs) were stimulated with lipopolysaccharide (LPS) to mimic the process of inflammation. The proliferation of the HPDLFs and the expression of alpha1-AR and beta2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1beta, IL-6 and IL-8 were detected after pretreatment with the alpha1/beta2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, alpha1-AR and beta2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of alpha1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of alpha1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1beta, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an alpha1-adrenergic signaling-mediated inflammatory response. We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.

MeSH Terms

Adrenergic alpha-1 Receptor Antagonists/*therapeutic use
Animals
Cells, Cultured
Cytokines/immunology
Fibroblasts/immunology/pathology
Humans
Lipopolysaccharides/administration & dosage/immunology
Male
Periodontal Ligament/cytology/immunology/pathology
Periodontitis/*drug therapy/*etiology/immunology/pathology
Phentolamine/*therapeutic use
Rats
Rats, Wistar
Receptors, Adrenergic, alpha-1/analysis/*immunology
Signal Transduction/drug effects
*Stress, Physiological/drug effects
Tyrosine 3-Monooxygenase/analysis/immunology
Adrenergic alpha-1 Receptor Antagonists
Cytokines
Lipopolysaccharides
Phentolamine
Receptors, Adrenergic, alpha-1
Tyrosine 3-Monooxygenase