Silencing SOX11 Alleviates Allergic Rhinitis by Inhibiting Epithelial-Derived Cytokines

Balkan Med J. 2023 Jan 23;40(1):57-65. doi: 10.4274/balkanmedj.galenos.2022.2022-9-31. Epub 2022 Dec 26.

Abstract

Background: Allergic rhinitis is a chronic inflammatory disease of the nasal mucosa affecting the quality of life of patients. SRY-box transcription factor 11 (SOX11) was reported to play important roles in inflammatory responses, but its role in AR is poorly understood.

Aims: To explore the role of SOX11 in the development of allergic rhinitis.

Study design: Cell culture and animal study.

Methods: An in vivo murine allergic rhinitis model was established using ovalbumin treatment in female mice. Interleukin-13-stimulated human nasal mucosa epithelial cells were used for in vitro studies. Expression levels of SOX11, epithelial-derived cytokines, and mucin were determined in both modesls.

Results: SOX11 was highly expressed in allergic rhinitis mice. Allergy symptoms, serum ovalbumin-specific IgE, histamine, eosinophils, goblet cells, and type 2 cytokine secretion were increased in ovalbumin-treated mice. Furthermore, allergic rhinitis mice exhibited overproduction of epithelial-derived cytokines (thymic stromal lymphopoietin, interleukin-25, interleukin-33), C-C motif chemokine ligand 26 (CCL26), and mucin 5 AC (MUC5AC). Silencing SOX11 alleviated the behavioral symptoms and upregulation of epithelial-derived cytokines, CCL26, and MUC5AC. In human nasal mucosa epithelial cells, interleukin-13 enhanced SOX11 expression in a time-dependent manner, and signal transducer and activator of transcription 6 (STAT6) was involved in the interleukin-13-mediated expression of SOX11 by regulating transcription. Knockdown of SOX11 reduced epithelial-derived cytokine expression and MUC5AC levels in interleukin-13-treated human nasal mucosa epithelial cells.

Conclusion: SOX11 plays a critical role in allergic rhinitis development by regulating epithelial-derived cytokines and might be a new therapeutic target for allergic rhinitis.

MeSH terms

  • Animals
  • Cytokines* / metabolism
  • Cytokines* / therapeutic use
  • Female
  • Humans
  • Interleukin-13 / pharmacology
  • Interleukin-13 / therapeutic use
  • Mice
  • Mucins / therapeutic use
  • Ovalbumin / pharmacology
  • Ovalbumin / therapeutic use
  • Quality of Life
  • Rhinitis, Allergic*
  • SOXC Transcription Factors

Substances

  • Cytokines
  • Interleukin-13
  • Ovalbumin
  • Mucins
  • SOX11 protein, human
  • SOXC Transcription Factors
  • Sox11 protein, mouse