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Blockade of cysteinyl leukotriene receptor 1 alleviates asthma by inhibiting bronchial epithelial cell apoptosis and activating the Nrf2 signaling pathway

  • Authors:
    • Xiangjie Wu
    • Yiqiong Chen
    • Suping Chen
    • Yiping Lin
  • View Affiliations / Copyright

    Affiliations: Department of Pediatrics, School of Medicine, Jinhua Polytechnic, Jinhua, Zhejiang 321007, P.R. China, Department of Pediatrics, School of Medicine, Jinhua Polytechnic, Jinhua, Zhejiang 321007, P.R. China
    Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 30
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    Published online on: December 13, 2024
       https://doi.org/10.3892/etm.2024.12780
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Abstract

The therapeutic role of blockade of cysteinyl leukotriene receptor 1 (CysLTR1) in asthma has been previously studied. However, the effect of CysLTR1 blockade on bronchial epithelial cell apoptosis and the nuclear factor erythroid‑derived 2‑related factor 2 (Nrf2) signaling pathway remains unclear. The present study established an ovalbumin (OVA)‑induced asthmatic rat model. Varying doses (1, 4 and 30 mg/kg) of montelukast sodium, a specific CysLTR1 antagonist, were used to inhibit CysLTR1 function in an asthmatic rat model. Reverse transcription‑quantitative PCR was used to detect the expression levels of CysLTR1, NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO‑1). CysLTR1 and Nrf2 protein expression levels were determined using western blotting. Immunofluorescence assays were used to evaluate the relative fluorescence intensity of Nrf2 in rat lung tissues. Lung tissue histology was assessed through hematoxylin & eosin, alcian blue and periodic acid‑Schiff and Masson's trichrome staining assays. The levels of IL‑17, IL‑4, serum IgE and the reduced/oxidized glutathione ratio were determined using ELISA assay kits. The number of inflammatory cells was analyzed using Wright‑Giemsa staining. Bronchial epithelial cell apoptosis was measured using a TUNEL assay. The results indicated that OVA‑induced inflammatory responses and increased eosinophil, lymphocyte and macrophage counts were significantly attenuated following blockade of CysLTR1. Downregulated expression of antioxidant genes NQO1 and HO‑1 and the reduced GSH/GSSG ratio caused by OVA challenge were restored by blockade of CysLTR1. Additionally, CysLTR1 blockade also reduced collagen deposition, suppressed goblet cell hyperplasia and inhibited bronchial epithelial cell apoptosis in a rat model of asthma. Furthermore, it was demonstrated that the blockade of CysLTR1 could significantly increase Nrf2 expression. In conclusion, the blockade of CysLTR1 could alleviate asthma in an OVA‑induced rat model by inhibiting bronchial epithelial cell apoptosis and activating the Nrf2 signaling pathway. These data may potentially provide a theoretical basis for future asthma therapy in a clinical setting.
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Copy and paste a formatted citation
Spandidos Publications style
Wu X, Chen Y, Chen S and Lin Y: Blockade of cysteinyl leukotriene receptor 1 alleviates asthma by inhibiting bronchial epithelial cell apoptosis and activating the Nrf2 signaling pathway. Exp Ther Med 29: 30, 2025.
APA
Wu, X., Chen, Y., Chen, S., & Lin, Y. (2025). Blockade of cysteinyl leukotriene receptor 1 alleviates asthma by inhibiting bronchial epithelial cell apoptosis and activating the Nrf2 signaling pathway. Experimental and Therapeutic Medicine, 29, 30. https://doi.org/10.3892/etm.2024.12780
MLA
Wu, X., Chen, Y., Chen, S., Lin, Y."Blockade of cysteinyl leukotriene receptor 1 alleviates asthma by inhibiting bronchial epithelial cell apoptosis and activating the Nrf2 signaling pathway". Experimental and Therapeutic Medicine 29.2 (2025): 30.
Chicago
Wu, X., Chen, Y., Chen, S., Lin, Y."Blockade of cysteinyl leukotriene receptor 1 alleviates asthma by inhibiting bronchial epithelial cell apoptosis and activating the Nrf2 signaling pathway". Experimental and Therapeutic Medicine 29, no. 2 (2025): 30. https://doi.org/10.3892/etm.2024.12780
Copy and paste a formatted citation
x
Spandidos Publications style
Wu X, Chen Y, Chen S and Lin Y: Blockade of cysteinyl leukotriene receptor 1 alleviates asthma by inhibiting bronchial epithelial cell apoptosis and activating the Nrf2 signaling pathway. Exp Ther Med 29: 30, 2025.
APA
Wu, X., Chen, Y., Chen, S., & Lin, Y. (2025). Blockade of cysteinyl leukotriene receptor 1 alleviates asthma by inhibiting bronchial epithelial cell apoptosis and activating the Nrf2 signaling pathway. Experimental and Therapeutic Medicine, 29, 30. https://doi.org/10.3892/etm.2024.12780
MLA
Wu, X., Chen, Y., Chen, S., Lin, Y."Blockade of cysteinyl leukotriene receptor 1 alleviates asthma by inhibiting bronchial epithelial cell apoptosis and activating the Nrf2 signaling pathway". Experimental and Therapeutic Medicine 29.2 (2025): 30.
Chicago
Wu, X., Chen, Y., Chen, S., Lin, Y."Blockade of cysteinyl leukotriene receptor 1 alleviates asthma by inhibiting bronchial epithelial cell apoptosis and activating the Nrf2 signaling pathway". Experimental and Therapeutic Medicine 29, no. 2 (2025): 30. https://doi.org/10.3892/etm.2024.12780
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