Upper Airway Chronic Inflammatory Diseases Laboratory, Korea University College of Medicine, Seoul, South Korea.
Medical Device Usability Test Center, Guro Hospital, Korea University College of Medicine, Seoul, South Korea.
Front Immunol. 2022 Mar 2;13:777928. doi: 10.3389/fimmu.2022.777928. eCollection 2022.
Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis (CRS) and is a refractory or intractable disease. However, a reliable clinical marker or an effective treatment strategy has not yet been established. ECRS is accompanied by excessive eosinophil infiltration and Th2 inflammatory response, which is closely related to tissue remodeling in the upper airways.
We sought to investigate the effect of eosinophils on tissue remodeling in ECRS. The purpose of this study was to identify the effects of eosinophils on the expression of pro-inflammatory mediators and extracellular matrix (ECM) in nasal fibroblasts and the key mediators that stimulate them.
Butyric acid was used to differentiate EOL-1 cells into eosinophils. We co-cultured differentiated EOL-1 cells and fibroblasts to measure the expression of pro-inflammatory mediators and ECM in fibroblasts. Among the cytokines secreted from the differentiated EOL-1 cells, factors that induced tissue remodeling of fibroblasts were identified.
Treatment with butyric acid (BA) differentiated EOL-1 cells into eosinophils. Differentiated EOL-1 cells induced fibroblasts to produce pro-inflammatory mediators, IL-6 and IL-8, and tissue remodeling factor, VEGF. It also induced myofibroblast differentiation and overexpression of ECM components. Differentiated EOL-1 cells overexpressed osteopontin (OPN), and recombinant OPN increased the expression of IL-6, IL-8, VEGF, and ECM components in nasal fibroblast. OPN was overexpressed in the nasal tissue of patients with ECRS and was associated with the severity of CRS.
Eosinophil-derived OPN stimulated nasal fibroblasts and contributed to inflammation and tissue remodeling in ECRS. Moreover, the expression level of OPN was proportional to the severity of ECRS. Therefore, OPN regulation is a potential treatment for ECRS.
嗜酸性慢性鼻-鼻窦炎（ECRS）是慢性鼻-鼻窦炎（CRS）的一种亚型，是一种难治性或顽固性疾病。然而，尚未建立可靠的临床标志物或有效的治疗策略。ECRS 伴有嗜酸性粒细胞浸润和 Th2 炎症反应，这与上呼吸道的组织重塑密切相关。
我们旨在研究嗜酸性粒细胞对 ECRS 中组织重塑的影响。本研究旨在确定嗜酸性粒细胞对鼻成纤维细胞中促炎介质和细胞外基质（ECM）表达的影响，以及刺激它们的关键介质。
使用丁酸将 EOL-1 细胞分化为嗜酸性粒细胞。我们共培养分化的 EOL-1 细胞和成纤维细胞，以测量成纤维细胞中促炎介质和 ECM 的表达。在分化的 EOL-1 细胞分泌的细胞因子中，鉴定出能诱导成纤维细胞组织重塑的因子。
丁酸（BA）处理可将 EOL-1 细胞分化为嗜酸性粒细胞。分化的 EOL-1 细胞诱导成纤维细胞产生促炎介质 IL-6 和 IL-8，以及组织重塑因子 VEGF。它还诱导肌成纤维细胞分化和 ECM 成分的过度表达。分化的 EOL-1 细胞过表达骨桥蛋白（OPN），重组 OPN 增加了鼻成纤维细胞中 IL-6、IL-8、VEGF 和 ECM 成分的表达。ECRS 患者的鼻组织中过表达 OPN，并且与 CRS 的严重程度相关。
嗜酸性粒细胞衍生的 OPN 刺激鼻成纤维细胞，促进 ECRS 中的炎症和组织重塑。此外，OPN 的表达水平与 ECRS 的严重程度成正比。因此，OPN 调节可能是 ECRS 的一种潜在治疗方法。
