Budesonide repairs decreased barrier integrity of eosinophilic nasal polyp epithelial cells caused by PM2.5

Siyuan Ma; Mu Xian; Yang Wang; Chengshuo Wang; Luo Zhang

doi:10.1002/clt2.12029

Budesonide repairs decreased barrier integrity of eosinophilic nasal polyp epithelial cells caused by PM_2.5

Clin Transl Allergy. 2021 Jul 3;11(5):e12019. doi: 10.1002/clt2.12029. eCollection 2021 Jul.

Authors

Siyuan Ma^{1

2

3}, Mu Xian^{1

2

3}, Yang Wang^{2

3}, Chengshuo Wang^{1

2

3}, Luo Zhang^{1

2

3

4}

Affiliations

¹ Department of Otolaryngology Head and Neck Surgery Beijing TongRen Hospital Capital Medical University Beijing China.
² Beijing Key Laboratory of Nasal Diseases Beijing Institute of Otolaryngology Beijing China.
³ Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases Chinese Academy of Medical Sciences Beijing China.
⁴ Department of Allergy Beijing TongRen Hospital Capital Medical University Beijing China.

Abstract

Background: Eosinophilic chronic rhinitis with nasal polyps (eos-CRSwNP) is a subtype of nasal polyps (NPs) characterized by severe type-2 inflammation and defective epithelial barrier function. The epithelial barrier plays important roles in the pathogenesis of NPs and type-2 inflammation. Particular matter 2.5 (PM_2.5) are fine particles with a diameter less than 2.5 μm, containing a mixture of different components. Here, we investigated the impact of PM_2.5 on the barrier function of the eos-CRSwNP epithelium and explored the reparative function of budesonide.

Methods: Samples from noninflammatory nasal mucosa and eos-CRSwNP were collected to establish an in vitro air-liquid interface cultured model. The cells were exposed to PM_2.5 at 50 or 100 µg/ml intermittently for 72 h, with or without budesonide pretreatment. Barrier function and tight junction (TJ) expression were reflected by measuring transepithelial resistance (TER), paracellular flux permeability of fluorescein isothiocyanate-labeled 4-kDa dextran, quantitative real-time polymerase chain reaction (qPCR), and immunofluorescence staining of TJ proteins. Cytokine expression was measured by qPCR and enzyme-linked immunosorbent assay or Luminex.

Results: PM_2.5 increased paracellular flux and downregulated TJ protein expression (zona occuldens-1, occludin, and claudin-1), but did not change TER. These changes could be partially restored by budesonide treatment. Interleukin (IL)-8, IL-10, IL-1α, and tissue inhibitor of metalloproteinase (TIMP)-1 concentrations were significantly increased in the culture medium of cells exposed to PM_2.5, and budesonide significantly reduced the changes in IL-8, IL-1α, and TIMP-1.

Conclusion: PM_2.5 impaired the barrier function of eos-CRSwNP epithelial cells and increased the permeability of large molecules. PM_2.5 also increased the secretion of pro-inflammatory cytokines by nasal epithelial cells. Budesonide could partially repair the damage, suggesting potential applications in clinical practice.

Keywords: budesonide; epithelial cells; nasal barrier; particular matter 2.5; type‐2 inflammation.