Chen Xiumin, Chen Changhui, Tu Zhaoxu, Guo Zeling, Lu Tong, Li Jian, Wen Yihui, Chen Dehua, Lei Wenbin, Wen Weiping, Li Hang
Department of Otorhinolaryngology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Otorhinolaryngology Hospital, Sun Yat-sen University, Guangzhou, China.
Cell Death Discov. 2024 May 2;10(1):213. doi: 10.1038/s41420-024-01980-x.
Allergic airway inflammation (AAI), including allergic rhinitis (AR) and allergic asthma, is driven by epithelial barrier dysfunction and type 2 inflammation. However, the underlying mechanism remains uncertain and available treatments are constrained. Consequently, we aim to explore the role of cell-free DNA (cfDNA) in AAI and assess the potential alleviating effects of cationic polymers (CPs) through cfDNA elimination. Levels of cfDNA were evaluated in AR patients, allergen-stimulated human bronchial epithelium (BEAS-2B cells) and primary human nasal epithelium from both AR and healthy control (HC), and AAI murine model. Polyamidoamine dendrimers-generation 3 (PAMAM-G3), a classic type of cationic polymers, were applied to investigate whether the clearance of cfDNA could ameliorate airway epithelial dysfunction and inhibit AAI. The levels of cfDNA in the plasma and nasal secretion from AR were higher than those from HC (P < 0.05). Additionally, cfDNA levels in the exhaled breath condensate (EBC) were positively correlated with Interleukin (IL)-5 levels in EBC (R = 0.4191, P = 0.0001). Plasma cfDNA levels negatively correlated with the duration of allergen immunotherapy treatment (R = -0.4297, P = 0.006). Allergen stimulated cfDNA secretion in vitro (P < 0.001) and in vivo (P < 0.0001), which could be effectively scavenged with PAMAM-G3. The application of PAMAM-G3 inhibited epithelial barrier dysfunction in vitro and attenuated the development of AAI in vivo. This study elucidates that cfDNA, a promising biomarker for monitoring disease severity, aggravates AAI and the application of intranasal PAMAM-G3 could potentially be a novel therapeutic intervention for AAI. Allergen stimulates the secretion of cell-free DNA (cfDNA) in both human and mouse airway. Intranasal polyamidoamine dendrimers-generation 3 (PAMAM-G3) scavenges cfDNA and alleviates allergic airway inflammation.
过敏性气道炎症（AAI），包括变应性鼻炎（AR）和过敏性哮喘，是由上皮屏障功能障碍和2型炎症驱动的。然而，其潜在机制仍不确定，且现有治疗方法有限。因此，我们旨在探讨游离DNA（cfDNA）在AAI中的作用，并评估阳离子聚合物（CPs）通过清除cfDNA的潜在缓解效果。在AR患者、变应原刺激的人支气管上皮细胞（BEAS-2B细胞）以及AR和健康对照（HC）的原代人鼻上皮细胞和AAI小鼠模型中评估cfDNA水平。应用第3代聚酰胺-胺树枝状大分子（PAMAM-G3），一种经典的阳离子聚合物，来研究cfDNA的清除是否能改善气道上皮功能障碍并抑制AAI。AR患者血浆和鼻分泌物中的cfDNA水平高于HC患者（P < 0.05）。此外，呼出气冷凝液（EBC）中的cfDNA水平与EBC中的白细胞介素（IL）-5水平呈正相关（R = 0.4191，P = 0.0001）。血浆cfDNA水平与变应原免疫治疗的持续时间呈负相关（R = -0.4297，P = 0.006）。变应原在体外（P < 0.001）和体内（P < 0.零零零零1）刺激cfDNA分泌，而PAMAM-G3可以有效清除cfDNA。PAMAM-G3的应用在体外抑制上皮屏障功能障碍，并在体内减轻AAI的发展。本研究表明，cfDNA是一种有前景的监测疾病严重程度的生物标志物，它会加重AAI，鼻内应用PAMAM-G3可能是AAI的一种新型治疗干预措施。变应原刺激人和小鼠气道中游离DNA（cfDNA）的分泌。鼻内应用第3代聚酰胺-胺树枝状大分子（PAMAM-G3）可清除cfDNA并减轻过敏性气道炎症。
