C/EBP β Mediates Endoplasmic Reticulum Stress Regulated Inflammatory Response and Extracellular Matrix Degradation in LPS-Stimulated Human Periodontal Ligament Cells

Int J Mol Sci. 2016 Mar 22;17(3):385. doi: 10.3390/ijms17030385.

Abstract

Periodontitis is an oral inflammatory disease that not only affects the integrity of local tooth-supporting tissues but also impacts systemic health. A compositional shift in oral microbiota has been considered as the main cause of periodontitis; however, the potential mechanism has not been fully defined. Herein, we investigated the role of CCAAT/enhancer-binding protein β (C/EBP β), a member of the C/EBP family of transcription factors, in human periodontal ligament cells (hPDLCs) exposed to Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS). RT-PCR and Western blotting analysis showed that the expression of C/EBP β was significantly increased in hPDLCs stimulated with LPS stimuli. Overexpression of C/EBP β by the recombinant adenoviral vector pAd/C/EBP β markedly increased the expression of the pro-inflammatory cytokines IL-6 and IL-8, and matrix metalloproteinases (MMP)-8 and -9 in hPDLCs in response to LPS. Furthermore, the activation of endoplasmic reticulum (ER) stress was confirmed in LPS-stimulated hPDLCs by measuring the expression of the ER stress marker molecules protein kinase-like ER kinase (PERK), eIF2α, GRP78/Bip, and C/EBP homologous protein (CHOP). The ER stress inhibitor salubrinal repressed, but inducer tunicamycin enhanced, the production of IL-6, IL-8, MMP-8, and MMP-9 in hPDLCs. Additionally, ER stress inducer tunicamycin significantly increased the expression level of C/EBP β in hPDLCs. Blocking of C/EBP β by siRNA resulted in a significant decrease in the secretion of IL-6 and IL-8 and expression of MMP-8 and MMP-9 induced by tunicamycin treatment in hPDLCs. Taken together, ER stress appears to play a regulatory role in the inflammatory response and extracellular matrix (ECM) degradation in hPDLCs in response to LPS stimuli by activating C/EBP β expression. This enhances our understanding of human periodontitis pathology.

Keywords: C/EBP β; P. gingivalis LPS; endoplasmic reticulum stress; human periodontal ligament cells; periodontitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCAAT-Enhancer-Binding Protein-beta / drug effects*
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • Cytokines / genetics
  • Endoplasmic Reticulum Stress / drug effects*
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix / microbiology
  • Extracellular Matrix / pathology
  • Humans
  • Inflammation / chemically induced
  • Inflammation / microbiology
  • Lipopolysaccharides / adverse effects
  • Lipopolysaccharides / pharmacology*
  • Matrix Metalloproteinases / genetics
  • Periodontal Ligament / cytology*
  • Periodontal Ligament / metabolism
  • Periodontal Ligament / microbiology
  • Periodontal Ligament / pathology
  • Porphyromonas gingivalis
  • Signal Transduction
  • Up-Regulation

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • CEBPB protein, human
  • Cytokines
  • Lipopolysaccharides
  • Matrix Metalloproteinases