Human periodontal ligament fibroblast (HPDLF) is a major component of the resident cells in the periodontal microenvironment, and plays important roles in periodontitis through multiple mechanisms. Although lipopolysaccharide (LPS) has been shown to cause endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR) in HPDLF, the mechanisms governing HPDLF function in periodontitis are unclear. In this study, we tested the ability of unfolded protein response (UPR) to regulate HPDLF in vitro and examined the underlying mechanisms. We found LPS-pretreated HPDLF induced macrophage polarization toward M1 phenotype. UPR activation reduced the inflammatory cytokine production and downregulated the expression of TLR4 in HPDLF. The phosphorylation of NF-κB p65 and I-κB was also inhibited by UPR activation. Our findings demonstrate that the connection of LPS, UPR, and HPDLF may represent a new concrete theory of innate immunity regulation in periodontal diseases, and suggest that targeting of UPR in HPDLF may be developed as a potent therapy for periodontitis.

人牙周膜成纤维细胞（HPDLF）是牙周微环境中驻留细胞的主要成分，通过多种机制在牙周炎中发挥重要作用。尽管脂多糖 (LPS) 已被证明会引起内质网 (ER) 应激并激活 HPDLF 中未折叠蛋白反应 (UPR)，但在牙周炎中控制 HPDLF 功能的机制尚不清楚。在这项研究中，我们测试了未折叠蛋白反应 (UPR) 在体外调节 HPDLF 的能力并检查了潜在的机制。我们发现 LPS 预处理的 HPDLF 诱导巨噬细胞向 M1 表型极化。UPR 激活减少了炎性细胞因子的产生并下调了 HPDLF 中 TLR4 的表达。NF-κB p65 和 I-κB 的磷酸化也被 UPR 激活抑制。