Department of Paediatrics, Xinhua Hospital Affiliated To Shanghai Jiao Tong University School Of Medicine, Shanghai, China.
Department of Paediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Bioengineered. 2021 Dec;12(1):3029-3039. doi: 10.1080/21655979.2021.1940622.
Asthma is mentioned as a chronic airway inflammatory disease, whose pathogenesis is complicated. The promotion of inflammation in asthma by IL-17A and IL-17F has been confirmed. In addition to covalent homodimers, both cytokines are also able to form heterodimers, further inducing downstream pathways via binding to the IL-17RA and IL-17RC receptor complex. In recent years, IL-17RA and its signal transduction pathway have been extensively researched. IL-17RC, however, remains relatively unexplored. In the present study, we self-assembled chitosan (CS) nanoparticles for intranasal delivery of recombinant protein IL-17RC (rIL-17RC) and preliminarily investigated its effect on a murine model of allergic asthma induced by ovalbumin (OVA). rIL-17RC was produced by the prokaryotic expression system and encapsulated into the CS nanoparticles via ionic cross-linking technique. The results showed that CS-RC nanoparticles via intranasal intervention significantly caused inhibition of mucus secretion and airway inflammatory cell infiltration, and reduced IL-4, IL-17, IL-17F levels in BALF. Hence, delivering receptor proteins such as IL-17RC, through CS nanoparticles as a carrier, could be an attractive therapeutic intervention for asthma.
哮喘被认为是一种慢性气道炎症性疾病,其发病机制较为复杂。IL-17A 和 IL-17F 促进哮喘炎症的作用已得到证实。除了共价同二聚体外,这两种细胞因子还能够形成异二聚体,通过与 IL-17RA 和 IL-17RC 受体复合物结合,进一步诱导下游途径。近年来,IL-17RA 及其信号转导途径得到了广泛研究。然而,IL-17RC 仍然相对未被探索。在本研究中,我们通过自组装壳聚糖(CS)纳米粒,进行重组蛋白 IL-17RC(rIL-17RC)的鼻腔给药,并初步研究了其对卵清蛋白(OVA)诱导的过敏性哮喘小鼠模型的影响。rIL-17RC 通过原核表达系统产生,并通过离子交联技术包封到 CS 纳米粒中。结果表明,鼻腔干预的 CS-RC 纳米粒显著抑制了黏液分泌和气道炎症细胞浸润,并降低了 BALF 中的 IL-4、IL-17 和 IL-17F 水平。因此,通过 CS 纳米粒作为载体递呈受体蛋白(如 IL-17RC)可能是一种有吸引力的哮喘治疗干预手段。