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UPR attenuates the proinflammatory effect of HPDLF on macrophage polarization

Cell Stress and Chaperones volume 26, pages 937–944 (2021)Cite this article

Abstract

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.

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Funding

This work was supported by the National Natural Science Foundation of China (82171848, 81971752, 81872315) and the Fourth Military Medical University projects (No. 2018HKPY02).

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Authors and Affiliations

  1. Department of Immunology, the Fourth Military Medical University, Xi’an, 710032, China

    Yuting Shen, Ying Wang, Zhaoyue Fu, Qianli Ma, Yun Song, Liang Fang & Lihua Chen

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  1. Yuting Shen
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  2. Ying Wang
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  3. Zhaoyue Fu
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  4. Qianli Ma
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  5. Yun Song
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  6. Liang Fang
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  7. Lihua Chen
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Correspondence to Liang Fang or Lihua Chen.

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Shen, Y., Wang, Y., Fu, Z. et al. UPR attenuates the proinflammatory effect of HPDLF on macrophage polarization. Cell Stress and Chaperones 26, 937–944 (2021). https://doi.org/10.1007/s12192-021-01234-0

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  • DOI: https://doi.org/10.1007/s12192-021-01234-0

Keywords

  • UPR
  • Periodontitis
  • LPS
  • HPDLF
  • Macrophage