Department of Otolaryngology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
Am J Rhinol Allergy. 2010 Jan-Feb;24(1):17-20. doi: 10.2500/ajra.2010.24.3381.
Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is an airway epithelial cell-derived molecule exerting host defense against pathogen. However, the function and regulation of SPLUNC1 in nasal epithelial cells are still unclear. Chronic rhinosinusitis with nasal polyps (CRSwNPs) is a disorder characterized by eosinophilic Th2 inflammation and frequent microbial colonization. The pathogenesis has been postulated as a disturbed mucosal immune response. This study investigates the SPLUNC1 expression of nasal polyp epithelial cells in air-liquid interface (ALI) culture and after treating with Th2 inflammatory cytokines IL-13.
Human nasal polyp epithelial cells isolated from patients with CRSwNPs were put in different cell culture models at days 0 and 21 and were assessed for expression of SPLUNC1 by microarray. Cultured cells in ALI plus retinoic acid (ALI + RA) model were then incubated with 0, 1, 10, and 100 ng/mL human recombinant IL-13 for up to 5 days. The expression of SPLUNC1 was assessed by real-time quantitative polymerase chain reaction (RT-Q-PCR), reverse-transcriptase PCR (RT-PCR) and Western blot analysis.
ALI + RA culture model harvesting ciliary differentiated nasal epithelial cells constitutively expressed high levels of SPLUNC1. In contrast, SPLUNC1 is reduced under classic submerged single layer culture. SPLUNC1 is also dose-responsively down-regulated after incubation with IL-13.
A microenvironmental milieu containing IL-13 may be detrimental to the host innate immunity response, at least in part, through the inhibition of SPLUNC1 production.
短 palate、lung 和 nasal epithelium clone 1（SPLUNC1）蛋白是一种气道上皮细胞衍生的分子，可发挥宿主防御作用，抵御病原体。然而，SPLUNC1 在鼻上皮细胞中的功能和调节仍不清楚。伴有鼻息肉的慢性鼻-鼻窦炎（CRSwNPs）是一种以嗜酸性 Th2 炎症和频繁微生物定植为特征的疾病。其发病机制被推测为黏膜免疫反应失调。本研究调查了鼻息肉上皮细胞在气-液界面（ALI）培养和用 Th2 炎症细胞因子 IL-13 处理后的 SPLUNC1 表达。
从患有 CRSwNPs 的患者中分离出的人鼻息肉上皮细胞分别在第 0 天和第 21 天置于不同的细胞培养模型中，并通过微阵列评估 SPLUNC1 的表达。然后，在 ALI + 视黄酸（ALI + RA）模型中培养的细胞用 0、1、10 和 100 ng/mL 人重组 IL-13 孵育长达 5 天。通过实时定量聚合酶链反应（RT-Q-PCR）、逆转录-PCR（RT-PCR）和 Western blot 分析评估 SPLUNC1 的表达。
ALI + RA 培养模型收获的纤毛分化鼻上皮细胞持续表达高水平的 SPLUNC1。相比之下，在经典的单层浸没培养下 SPLUNC1 减少。用 IL-13 孵育后，SPLUNC1 也呈剂量依赖性下调。
含有 IL-13 的微环境可能至少部分通过抑制 SPLUNC1 的产生对宿主先天免疫反应造成损害。
