Chronic stress enhances progression of periodontitis via alpha 1-adrenergic signaling: a potential target for periodontal disease therapy

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 alpha 1-adrenergic receptor ( alpha 1-AR) and beta 2-adrenergic receptor ( beta 2-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 alpha 1-AR and beta 2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1 beta , IL-6 and IL-8 were detected after pretreatment with the alpha 1/ beta 2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, alpha 1-AR and beta 2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of alpha 1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of alpha 1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1 beta , IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an alpha 1-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.