Fine particulate matter promotes airway inflammation and mucin production by activating endoplasmic reticulum stress and the IRE1α/NOD1/NF‑κB pathway

Hu,Lihua; Xu,Chaoqun; Tang,Xiang; Yu,Shanjun; Wang,Lijun; Li,Qi; Zhou,Xiangdong

doi:10.3892/ijmm.2023.5299

Fine particulate matter promotes airway inflammation and mucin production by activating endoplasmic reticulum stress and the IRE1α/NOD1/NF‑κB pathway

Authors:
- Lihua Hu
- Chaoqun Xu
- Xiang Tang
- Shanjun Yu
- Lijun Wang
- Qi Li
- Xiangdong Zhou
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Affiliations: Department of Respiratory Medicine, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570102, P.R. China
Published online on: August 28, 2023 https://doi.org/10.3892/ijmm.2023.5299
Article Number: 96
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Fine particulate matter (PM2.5) is a type of small particle that is <2.5 µm in diameter that may cause airway inflammation. Thus, the present study aimed to explore the effects of PM2.5 on endoplasmic reticulum (ER) stress and airway inflammation in human airway epithelial cells. For this purpose, HBE135‑E6E7 airway epithelial cells were cultured and exposed to specific concentrations of PM2.5 for various periods of time, and cell viability was determined using a Cell Counting Kit‑8 assay. The results of the present study demonstrated that exposure to PM2.5 increased the mRNA and protein expression levels of interleukin (IL)‑6, tumor necrosis factor (TNF)‑α and mucin 5AC (MUC5AC). Moreover, the expression levels of ER stress‑related proteins, such as glucose‑regulated protein 78, CCAAT‑enhancer binding protein homologous protein, activating transcription factor 6, protein kinase R‑like ER kinase (PERK), phosphorylated (p‑)PERK, inositol‑requiring enzyme 1α (IRE1α) and p‑IRE1α, and nucleotide‑binding oligomerization domain 1 (NOD1) expression levels were increased following exposure to PM2.5. Transfection with IRE1α small interfering RNA (siRNA) led to the increased production of IL‑6, TNF‑α and MUC5AC. Moreover, the expression of NOD1 and the translocation of NF‑κB p65 were inhibited following transfection with IRE1α siRNA. In addition, the results of the present study demonstrated that transfection with NOD1 siRNA decreased the production of IL‑6, TNF‑α and MUC5AC, and decreased the translocation of NF‑κB p65. The expression levels of IL‑6, TNF‑α and MUC5AC were increased in the HBE135‑E6E7 cells following treatment with C12‑iE‑DAP, a NOD1 agonist. Moreover, treatment with C12‑iE‑DAP led to the activation of NF‑κB p65. Collectively, the results of the present study suggest that PM2.5 promotes airway inflammation and mucin production by activating ER stress in HBE135‑E6E7 airway epithelial cells, and that the IRE1α/NOD1/NF‑κB pathway may be involved in this process.

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