Viegas Joana, Cardoso Elsa M, Bonneau Lucile, Esteves Ana Filipa, Ferreira Catarina L, Alves Gilberto, Santos-Silva António Jorge, Vitale Marco, Arosa Fernando A, Taborda-Barata Luís
CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilhã, Portugal.
ESS-IPG-School of Health Sciences, Polytechnic Institute of Guarda, Rua da Cadeia, 6300-307 Guarda, Portugal.
Biomedicines. 2024 Feb 9;12(2):408. doi: 10.3390/biomedicines12020408.
Sulfurous thermal waters (STWs) are used as a complementary treatment for allergic rhinitis. However, there is scant data on the effects of STW on nasal epithelial cells, and in vitro models are warranted. The main aim of this study was to evaluate the dose and time effects of exposure to 3D nasal inserts (MucilAir-HF allergic rhinitis model) with STW or isotonic sodium chloride solution (ISCS) aerosols. Transepithelial electrical resistance (TEER) and histology were assessed before and after nebulizations. Chemokine/cytokine levels in the basal supernatants were assessed by enzyme-linked immunosorbent assay. The results showed that more than four daily nebulizations of four or more minutes compromised the normal epithelial integrity. In contrast, 1 or 2 min of STW or ISCS nebulizations had no toxic effect up to 3 days. No statistically significant changes in release of inflammatory chemokines MCP-1/CCL2 > IL-8/CXCL8 > MIP-1α/CCL3, no meaningful release of "alarmins" (IL-1α, IL-33), nor of anti-inflammatory IL-10 cytokine were observed. We have characterized safe time and dose conditions for aerosol nebulizations using a novel in vitro 3D nasal epithelium model of allergic rhinitis patients. This may be a suitable in vitro setup to mimic in vivo treatments of chronic rhinitis with STW upon triggering an inflammatory stimulus in the future.
硫磺温泉水（STWs）被用作变应性鼻炎的辅助治疗方法。然而，关于STW对鼻上皮细胞影响的数据很少，因此需要体外模型。本研究的主要目的是评估暴露于含有STW或等渗氯化钠溶液（ISCS）气雾剂的3D鼻插入物（MucilAir-HF变应性鼻炎模型）的剂量和时间效应。在雾化前后评估跨上皮电阻（TEER）和组织学。通过酶联免疫吸附测定法评估基础上清液中的趋化因子/细胞因子水平。结果表明，每天雾化超过四次且每次超过四分钟会损害正常的上皮完整性。相比之下，STW或ISCS雾化1或2分钟，长达3天均无毒性作用。未观察到炎症趋化因子MCP-1/CCL2>IL-8/CXCL8>MIP-1α/CCL3的释放有统计学显著变化，未观察到“警报素”（IL-1α、IL-33）有意义的释放，也未观察到抗炎性IL-10细胞因子的释放。我们使用一种新型的变应性鼻炎患者体外3D鼻上皮模型，确定了气雾剂雾化的安全时间和剂量条件。这可能是一种合适的体外设置，以便在未来触发炎症刺激时模拟用STW对慢性鼻炎进行的体内治疗。
