Up-regulation of the endoplasmic reticulum stress-response in periodontal disease

Clin Chim Acta. 2009 Mar;401(1-2):134-40. doi: 10.1016/j.cca.2008.12.007. Epub 2008 Dec 13.

Abstract

Background: Endoplasmic reticulum (ER) stress is the cell response by activation of the unfolded protein response (UPR) pathway in a variety of conditions such as infection and aging. The UPR may be associated with the pathogenesis of periodontal disease because of the induction of apoptosis and activation of nuclear factor-kappaB (NF-kappaB), a transcription factor for pro-inflammatory cytokines. However, the relationship between ER stress and periodontal disease is yet to be determined.

Methods: The expression of UPR-related molecules was analyzed by real-time polymerase chain reaction and immunohistochemistry, respectively and compared between gingivitis and periodontitis. The gene expressions were also analyzed for macrophages stimulated with lipopolysaccharides (LPS) from Escherichia coli (E. coli), and Porphyromonas gingivalis (P. gingivalis) or IFN-gamma.

Results: The expression levels of UPR-related genes and HSP60 were significantly higher in periodontitis compared with gingivitis lesions. However, LPS from P. gingivalis but not E. coli or IFN-gamma failed to up-regulate the gene expression in macrophage.

Conclusions: An inflammatory response may have profound effect on the UPR response, particularly in periodontitis patients. Considering the histological nature of periodontitis and the link between UPR and inflammatory responses via NF-kappaB, ER stress in B cells could be another pathological mechanism underlying periodontal disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis / drug effects
  • Caspases, Initiator / drug effects
  • Caspases, Initiator / metabolism
  • Cell Line
  • Chaperonin 60 / metabolism
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism*
  • Gingivitis / genetics
  • Gingivitis / metabolism*
  • Gingivitis / pathology
  • HSP70 Heat-Shock Proteins / metabolism
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-1beta / drug effects
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Middle Aged
  • Periodontitis / genetics
  • Periodontitis / metabolism*
  • Periodontitis / pathology
  • Up-Regulation / genetics

Substances

  • Chaperonin 60
  • HSP70 Heat-Shock Proteins
  • Interleukin-1beta
  • Lipopolysaccharides
  • Interferon-gamma
  • CASP4 protein, human
  • Caspases, Initiator