In Vitro Treatment with 2-APB Inhibits the Inflammation in Nasal Polyps

Lin Lin1, Fei Dai2, Zhongchun Chen2

  • 1Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital of Fudan University, Shanghai, China linlinhsn@aliyun.com.

Abstract

Insights

Investigating Orai1 in nasal polyps (NPs) revealed its upregulation. Inhibiting Orai1 with 2-aminoethoxydiphenyl borate (2-APB) reduced inflammatory mediators and mucins, suggesting Orai1 intervention may hinder NP development.

Area of Science:

  • Otorhinolaryngology
  • Immunology
  • Molecular Biology

Background:

  • Glucocorticoids are the primary treatment for chronic rhinosinusitis with nasal polyps (CRSwNP), but their efficacy is limited (60.9%-80%).
  • Novel therapeutic targets are needed for CRSwNP management.
  • Orai1, a calcium channel, is implicated in inflammatory processes.

Purpose of the Study:

  • To investigate Orai1 expression in nasal polyps (NPs).
  • To determine the effect of 2-aminoethoxydiphenyl borate (2-APB), an Orai1 inhibitor, on NPs in vitro.
  • To compare the efficacy of Orai1 intervention with dexamethasone (DEX) in CRSwNP models.

Main Methods:

  • Prospective cross-sectional study at a university hospital.
  • Nasal biopsy samples from CRSwNP patients and normal subjects.
  • Immunohistochemistry, Western blot, ELISA, and RT-PCR to analyze Orai1 expression.
  • In vitro treatment with DEX or 2-APB, followed by analysis of inflammatory mediators and mucins.

Main Results:

  • Orai1 expression was upregulated in NPs compared to normal nasal mucosa, localized to inflammatory and glandular cells.
  • 2-APB treatment significantly decreased Orai1 expression in NPs, while DEX did not.
  • 2-APB treatment resulted in greater reduction of inflammatory mediators (IL-1β, IL-5, ECP, LTC4, IFN-γ, sIgE) and mucins (MUC5B, MUC7) than DEX treatment.

Conclusions:

  • Orai1 plays a significant role in the formation and development of nasal polyps.
  • Intervention targeting Orai1 may represent a novel therapeutic strategy for inhibiting NP development.
  • Orai1 inhibition shows potential for more effective treatment of CRSwNP than current glucocorticoid therapy.