, Volume 41, Issue 2, pp 614–625 | Cite as

Protein Disulfide Isomerase Silence Inhibits Inflammatory Functions of Macrophages by Suppressing Reactive Oxygen Species and NF-κB Pathway

  • Yinbo Xiao
  • Chaohong Li
  • Minghui Gu
  • Haixing Wang
  • Weishen Chen
  • Guotian Luo
  • Guangpu Yang
  • Ziji Zhang
  • Yangchun Zhang
  • Guoyan Xian
  • Ziqing Li
  • Puyi Sheng


Macrophages play an essential role in inflammation. Protein disulfide isomerase (PDI) is central to the redox system, which is closely linked with the inflammatory function of macrophages. However, the relationship between PDI and inflammation is still unknown. In this study, we tested the effects of PDI on inflammatory responses in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). Using CRISPR/Cas9 system, we found that PDI knockout suppressed migration, M1 polarization, and secretion of tumor necrosis factor-α (TNF-α) and interluekin-6 (IL-6). The repression of these inflammatory processes was accompanied by decreased production of reactive oxygen species (ROS). PDI ablation also inactivated the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activated the phosphorylation of NF-κB inhibitor alpha (IκBα). These findings demonstrate that PDI knockout inhibits the inflammatory function of macrophages by decreasing ROS production and inactivating NF-κB pathway.


inflammation protein disulfide isomerase (PDI) CRISPR/Cas9 NF-κB reactive oxygen species (ROS) RAW 264.7 



We thank Chan Rong, Xiujian Lan, and Xuanhong Zhang (Department of Medical Science Experimentation Center, Sun Yat-sen University) for technical support.

Funding Information

This work was supported by the National Natural Science Foundation of China (No. 81171710 and No. 81672149) and Natural Science Foundation of Guangdong Province (No. 2015A030311004).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Yinbo Xiao
    • 1
  • Chaohong Li
    • 2
  • Minghui Gu
    • 1
  • Haixing Wang
    • 1
    • 3
  • Weishen Chen
    • 1
  • Guotian Luo
    • 1
    • 4
  • Guangpu Yang
    • 5
  • Ziji Zhang
    • 1
  • Yangchun Zhang
    • 1
  • Guoyan Xian
    • 1
  • Ziqing Li
    • 1
    • 6
  • Puyi Sheng
    • 1
  1. 1.Department of Joint SurgeryThe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouPeople’s Republic of China
  2. 2.Department of Histology and Embryology, Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouChina
  3. 3.Department of Orthopaedics and Traumatology, Faculty of MedicineThe Chinese University of Hong KongShatinChina
  4. 4.Laboratoire de Bioingénierie et Biomécanique Ostéo-articulaires, UMR CNRS 7052Faculté de Médecine Paris 7-Denis DiderotParisFrance
  5. 5.Department of Gastrointestinal SurgeryThe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina
  6. 6.Department of Anatomy and Cell Biology, Penn Dental MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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