2. Academic Validation
  3. NF-κB pathway affects silica nanoparticle-induced fibrosis via inhibited inflammatory response and epithelial-mesenchymal transition in 3D co-culture

NF-κB pathway affects silica nanoparticle-induced fibrosis via inhibited inflammatory response and epithelial-mesenchymal transition in 3D co-culture

  • Toxicol Lett. 2023 Jun 30;S0378-4274(23)00213-8. doi: 10.1016/j.toxlet.2023.06.014.
Xiaojing Yang 1,  Jing Zhang 2,  Min Xiong 3,  Yushan Yang 4,  Pan Yang 5,  Ning Li 6,  Fan Shi 7,  Yaxin Zhu 8,  Keyun Guo 9,  Yulan Jin 10
Affiliations

Affiliations

  • 1 School of Public Health, North China University of Science and Technology, Tangshan, Hebei, China. Electronic address: 1597911576@qq.com.
  • 2 School of Public Health, North China University of Science and Technology, Tangshan, Hebei, China. Electronic address: zhangjingluck89@126.com.
  • 3 School of Public Health, North China University of Science and Technology, Tangshan, Hebei, China. Electronic address: xx721013@126.com.
  • 4 School of Public Health, North China University of Science and Technology, Tangshan, Hebei, China. Electronic address: 790861192@qq.com.
  • 5 Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, Hubei, China. Electronic address: 992311814@qq.com.
  • 6 School of Public Health, North China University of Science and Technology, Tangshan, Hebei, China. Electronic address: Johnsonln93@163.com.
  • 7 School of Public Health, North China University of Science and Technology, Tangshan, Hebei, China. Electronic address: shifan@stu.ncst.edu.cn.
  • 8 School of Public Health, North China University of Science and Technology, Tangshan, Hebei, China. Electronic address: 1945217325@qq.com.
  • 9 School of Public Health, North China University of Science and Technology, Tangshan, Hebei, China. Electronic address: 1569841021@qq.com.
  • 10 School of Public Health, North China University of Science and Technology, Tangshan, Hebei, China. Electronic address: 13932579151@163.com.
PMID: 37394155 DOI: 10.1016/j.toxlet.2023.06.014
Abstract

Long-term inhalation of silica nanoparticles (SiNPs) can induce pulmonary fibrosis (PF), nevertheless, the potential mechanisms remain elusive. Herein, we constructed a three-dimensional (3D) co-culture model by using Matrigel to investigate the interaction among different cells and potential regulatory mechanisms after SiNPs exposure. Methodologically, we dynamically observed the changes in cell morphology and migration after exposure to SiNPs by co-culturing mouse monocytic macrophages (RAW264.7), human non-small cell lung Cancer cells (A549), and medical research council cell strain-5 (MRC-5) in Matrigel for 24h. Subsequently, we detected the expression of nuclear factor kappa B (NF-κB), inflammatory factor and epithelial-mesenchymal transition (EMT) markers. The results showed that SiNPs produced toxic effects on cells. In the 3D co-culture state, the cell's movement velocity and displacement increased, and the cell migration ability was enhanced. Meanwhile, the expression of inflammatory factor tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) were upregulated, the epithelial marker E-cadherin (E-cad) was downregulated, the mesenchymal marker N-Cadherin (N-cad) and myofibroblast marker alpha-smooth muscle actin (α-SMA) expression were upregulated, while NF-κB expression was also upregulated after SiNPs exposure. We further found that cells were more prone to transdifferentiate into myofibroblasts in the 3D co-culture state. Conversely, utilizing the NF-κB-specific inhibitor BAY 11-7082 effectively downregulated the expression of TNF-α, IL-6, interleukin-1β (IL-1β), N-cad, α-SMA, collagen-I (COL I), and fibronectin (FN), the expression of E-cad was upregulated. These findings suggest that NF-κB is involved in regulating SiNPs-induced inflammatory, EMT, and fibrosis in the 3D co-culture state.

Keywords

3D co-culture; Matrigel; NF-κB; Pulmonary fibrosis; SiNPs.

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