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Platelet-Activating Factor Disrupts the Nasal Epithelial Barrier Independently of the Platelet-Activating Factor Receptor Pathway
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DOI：10.4168/aair.2025.17.2.212.png)
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Abstract
En 中文
Purpose: Platelet-activating factor (PAF) mediates nasal congestion and rhinorrhea by affecting vascular permeability, but the underlying mechanisms remain unclear. Here, we sought to explore the effect of PAF on the nasal epithelial barrier in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Human nasal epithelial cells (hNECs) were pre-treated with Apafant, a PAF receptor (PAFR) inhibitor, or MCC950, an NOD-like receptor protein 3 (NLRP3) inflammasome inhibitor, before PAF stimulation. The nasal epithelial barrier function was assessed by measuring the transepithelial electrical resistance (TER) and sodium fluorescein flux. Additionally, the expression of mRNAs and proteins of tight junctions were assessed. Results: PAF significantly decreased TER and enhanced the fluorescein flux permeability in air-liquid interface cultures of hNECs, while also downregulating the expression of ZO-1, occludin, claudin-1, and claudin-4. However, the disruptive effect of PAF on the nasal epithelial barrier was attenuated by MCC950, but not by Apafant. Furthermore, MCC950 inhibited PAF-induced NLRP3 activation and its downstream molecules, including caspase-1, ASC, interleukin (IL)-1 beta, and IL-18. Conclusions: Our findings indicate that PAF has the potential to disrupt the nasal epithelial barrier in CRSwNP and may be linked to NLRP3 activation, while PAFR is not essential for this process. This discovery helps to explain why PAFR antagonists are ineffective in blocking PAF-mediated inflammation in clinical settings.
Keywords:
Rhinitis
sinusitis
nasal polyps
nasal mucosa
epithelial cells
platelet activating factor
zonula occludens-1 protein
occludin
claudins
caspases
interleukin-18
interleukin-1 beta
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1.1K
Citations:
2.7K
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