title: C/EBP β Mediates Endoplasmic Reticulum Stress Regulated Inflammatory Response and Extracellular Matrix Degradation in LPS-Stimulated Human Periodontal Ligament Cells.
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.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Pediatric Dentistry, School of Stomatology, the Fourth Military Medical University, Xi'an 710032, China. baiyudi@fmmu.edu.cn.
authors.forename: Yudi
authors.initials: Y
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Pediatric Dentistry, School of Stomatology, the Fourth Military Medical University, Xi'an 710032, China. yiweiywy@tom.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Pediatric Dentistry, School of Stomatology, the Fourth Military Medical University, Xi'an 710032, China. lianwulw@tom.com.
authors.forename: Lian
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, the Fourth Military Medical University, Xi'an 710032, China. jianhuaweijhw@163.com.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Pediatric Dentistry, School of Stomatology, the Fourth Military Medical University, Xi'an 710032, China. xiaojingwangxjw@163.com.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Health Statistics, the Fourth Military Medical University, Xi'an 710033, China. bai2010@fmmu.edu.cn.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Bai
mesh_terms: D022782:CCAAT-Enhancer-Binding Protein-beta / Q000187:drug effects* / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005109:Extracellular Matrix / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000382:microbiology; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000235:genetics; D010513:Periodontal Ligament / Q000166:cytology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016966:Porphyromonas gingivalis; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C545012:CEBPB protein, human; D016207:Cytokines; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D008070:Lipopolysaccharides; D020782:Matrix Metalloproteinases
keywords: C/EBP β; P. gingivalis LPS; endoplasmic reticulum stress; human periodontal ligament cells; periodontitis