title: Lipopolysaccharide Activates the Unfolded Protein Response in Human Periodontal Ligament Fibroblasts.
abstract: The activation of the unfolded protein response (UPR) has been demonstrated in periodontal diseases. However, the cellular and molecular mechanisms by which the UPR is induced in periodontitis remain unclear. In this study, the effects of lipopolysaccharide (LPS) on the induction of the UPR in human periodontal ligament fibroblasts (HPDLFs) in vitro are investigated.
  
  
  
  HPDLFs isolated from human PDLs were stimulated with various concentrations of Escherichia coli LPS (0.1, 1, and 10 μg/mL) for the indicated time points (0, 3, 6, 9, 12, and 18 hours). The messenger RNA (mRNA) and protein levels of molecular markers associated with UPR activation, such as glucose-regulated protein 78 (GRP78), X-box binding protein 1 (XBP1), and C/EBP homologous protein (CHOP), were measured at different time points of LPS treatment. Apoptosis of HPDLFs was assessed by Annexin V-FITC and propidium iodide staining, followed by flow cytometry.
  
  
  
  LPS treatment of HPDLFs increased GRP78 mRNA and protein levels in a concentration-dependent manner. Additionally, LPS also induced the expression, splicing, and activation of XBP1 mRNA. Moreover, LPS-induced CHOP expression was concentration dependent: a lower concentration of LPS (0.1 μg/mL) had no effect on CHOP mRNA levels, but higher concentrations of LPS (1 and 10 μg/mL) markedly increased CHOP mRNA and protein expression without inducing apoptosis.
  
  
  
  The findings demonstrate that activating the Toll-like receptor-4 signaling pathway in HPDLFs using LPS triggers the UPR in vitro, warranting additional investigation into the precise mechanisms by which pathways promote this response under inflammatory conditions.
authors.affiliation: State Key Laboratory of Military Stomatology, Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.|Department of Immunology, School of Basic Medicine, Fourth Military Medical University.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Immunology, School of Basic Medicine, Fourth Military Medical University.|Hospital of Hubei Armed Police Corps, Wuhan, Hubei, China.
authors.forename: Jiuyu
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Immunology, School of Basic Medicine, Fourth Military Medical University.
authors.forename: Hanyu
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Department of Immunology, School of Basic Medicine, Fourth Military Medical University.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Immunology, School of Basic Medicine, Fourth Military Medical University.
authors.forename: Boquan
authors.initials: B
authors.lastname: Jin
authors.affiliation: Department of Immunology, School of Basic Medicine, Fourth Military Medical University.
authors.forename: Lihua
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Military Stomatology, Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Qintao
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000091342:Endoplasmic Reticulum Chaperone BiP; D005347:Fibroblasts; D018840:HSP70 Heat-Shock Proteins; D006801:Humans; D008070:Lipopolysaccharides / Q000502:physiology*; D008565:Membrane Proteins; D010513:Periodontal Ligament / Q000378:metabolism*; D051742:Transcription Factor CHOP; D056811:Unfolded Protein Response
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C018551:glucose-regulated proteins; D051742:Transcription Factor CHOP
keywords: Lipopolysaccharides; periodontal diseases; unfolded protein response