C/EBP β Mediates Endoplasmic Reticulum Stress Regulated Inflammatory Response and Extracellular Matrix Degradation in LPS-Stimulated Human Periodontal Ligament Cells.
C/EBP β Mediates Endoplasmic Reticulum Stress Regulated Inflammatory Response and Extracellular Matrix Degradation in LPS-Stimulated Human Periodontal Ligament Cells.
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DOI：
10.3390/ijms17030385
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发表时间：
2016-03-22
影响因子：
5.6
通讯作者：
Bai Y
中科院分区：
文献类型：
--
作者：
Bai Y;Wei Y;Wu L;Wei J;Wang X;Bai Y
牙周炎是一种口腔炎症性疾病，不仅影响局部牙齿支持组织的完整性，还影响全身健康。口腔微生物区系的组成改变被认为是牙周炎的主要原因；然而，其潜在的机制还没有完全确定。在此，我们研究了C/eBP转录因子家族成员CCAAT/增强子结合蛋白β(C/eBPβ)在牙周膜细胞(HPDLCs)暴露于牙龈卟啉单胞菌脂多糖中的作用。RT-PCR法和Western blotting分析表明，脂多糖刺激后的人肺小管上皮细胞C/EBpβ表达明显增加。重组腺病毒载体pAD/C/eBPβ过表达C/eBPβ可显著增加脂多糖诱导的人肺小管上皮细胞中促炎细胞因子IL-6和IL-8以及基质金属蛋白酶-8和-9的表达。此外，通过检测内质网应激标志物蛋白激酶样激酶(PERK)、eIF2α、GRP78/BiP和C/EBP同源蛋白(CHOP)的表达，进一步证实内质网应激在内毒素刺激的hPDLCs中的激活。内质网应激抑制剂Salubrine抑制hPDLCs产生IL-6、IL-8、MMP8和MMP9，而诱导剂衣霉素促进其产生。此外，内质网应激诱导剂衣霉素显著增加人PDLCs中C/EBpβ的表达水平。小干扰RNA阻断C/EBPβ后，衣霉素诱导的hPDLCs分泌IL-6、IL-8及表达MMP8、MMP9明显减少。综上所述，内质网应激可能通过激活C/EBPβ的表达，在内毒素刺激下的炎症反应和细胞外基质降解中发挥调节作用。这加深了我们对人类牙周炎病理的理解。
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.