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Chronic stress enhances progression of periodontitis via α1-adrenergic signaling: a potential target for periodontal disease therapy.

Lu H, Xu M, Wang F, Liu S, Gu J, Lin S - Exp. Mol. Med. (2014)

Bottom Line: Phentolamine significantly reduced the inflammatory cytokine levels.Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of α1-ARfollowing LPS pretreatment.We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.

View Article: PubMed Central - PubMed

Affiliation: Department of Stomatology, Navy General Hospital, Beijing, China.

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 α1-adrenergic receptor (α1-AR) and β2-adrenergic receptor (β2-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 α1-AR and β2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1β, IL-6 and IL-8 were detected after pretreatment with the α1/β2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, α1-AR and β2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of α1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of α1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1β, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an α1-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.

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Related in: MedlinePlus

CS exposure increased the expression of the adrenergic receptor protein. G3 was treated with a series of unexpected chronic stresses for 4 weeks, and then, the protein levels of α1-AR (a), and β2-AR (b) were analyzed by western blotting. *compared with G1 P<0.01, #compared with G2 P<0.01.
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fig2: CS exposure increased the expression of the adrenergic receptor protein. G3 was treated with a series of unexpected chronic stresses for 4 weeks, and then, the protein levels of α1-AR (a), and β2-AR (b) were analyzed by western blotting. *compared with G1 P<0.01, #compared with G2 P<0.01.

Mentions: The ARs, particularly norepinephrine and epinephrine, are targets of catecholamines.20 To clarify the manner by which these stress-related biobehavioral factors accelerate the progression of periodontitis, a further analysis of the AR levels was performed. The α1-AR and β2-receptor (β2-AR) are generally considered to be involved in brain-immune communication. Therefore, we analyzed the protein levels of these two receptors in periodontal tissues with periodontitis with or without CS. As shown in Figure 2a, after periodontitis induction, the expression of α1-AR markedly increased in the periodontitis group (G2) (G1 versus G2; P<0.01), whereas the group with both periodontitis and CS (G3) exhibited even higher levels of α1-AR expression. However, the protein levels of β2-AR were similar between G1 and G2 (P>0.05) (Figure 2b) and only increased in G3. These protein expression data demonstrated that the inflammation (ligated sites) associated with CS resulted in significantly increased protein levels of both α1-AR and β2-AR (P<0.01) but that only the α1-AR response to inflammation was caused by simple periodontitis (G2). This suggests that α1-AR may have a more important role in the mechanisms underlying CS-accelerated periodontitis compared with β2-AR.


Chronic stress enhances progression of periodontitis via α1-adrenergic signaling: a potential target for periodontal disease therapy.

Lu H, Xu M, Wang F, Liu S, Gu J, Lin S - Exp. Mol. Med. (2014)

CS exposure increased the expression of the adrenergic receptor protein. G3 was treated with a series of unexpected chronic stresses for 4 weeks, and then, the protein levels of α1-AR (a), and β2-AR (b) were analyzed by western blotting. *compared with G1 P<0.01, #compared with G2 P<0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4221694&req=5

fig2: CS exposure increased the expression of the adrenergic receptor protein. G3 was treated with a series of unexpected chronic stresses for 4 weeks, and then, the protein levels of α1-AR (a), and β2-AR (b) were analyzed by western blotting. *compared with G1 P<0.01, #compared with G2 P<0.01.
Mentions: The ARs, particularly norepinephrine and epinephrine, are targets of catecholamines.20 To clarify the manner by which these stress-related biobehavioral factors accelerate the progression of periodontitis, a further analysis of the AR levels was performed. The α1-AR and β2-receptor (β2-AR) are generally considered to be involved in brain-immune communication. Therefore, we analyzed the protein levels of these two receptors in periodontal tissues with periodontitis with or without CS. As shown in Figure 2a, after periodontitis induction, the expression of α1-AR markedly increased in the periodontitis group (G2) (G1 versus G2; P<0.01), whereas the group with both periodontitis and CS (G3) exhibited even higher levels of α1-AR expression. However, the protein levels of β2-AR were similar between G1 and G2 (P>0.05) (Figure 2b) and only increased in G3. These protein expression data demonstrated that the inflammation (ligated sites) associated with CS resulted in significantly increased protein levels of both α1-AR and β2-AR (P<0.01) but that only the α1-AR response to inflammation was caused by simple periodontitis (G2). This suggests that α1-AR may have a more important role in the mechanisms underlying CS-accelerated periodontitis compared with β2-AR.

Bottom Line: Phentolamine significantly reduced the inflammatory cytokine levels.Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of α1-ARfollowing LPS pretreatment.We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.

View Article: PubMed Central - PubMed

Affiliation: Department of Stomatology, Navy General Hospital, Beijing, China.

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 α1-adrenergic receptor (α1-AR) and β2-adrenergic receptor (β2-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 α1-AR and β2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1β, IL-6 and IL-8 were detected after pretreatment with the α1/β2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, α1-AR and β2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of α1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of α1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1β, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an α1-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.

Show MeSH
Related in: MedlinePlus