Wang Ling-Feng, Chien Chen-Yu, Tai Chih-Feng, Chiang Feng-Yu, Chen Jeff Yi-Fu
Department of Otolaryngology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Otolaryngology, Faculty of Medicine, College of Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Otolaryngology, Faculty of Medicine, College of Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Otolaryngology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Kaohsiung J Med Sci. 2015 Feb;31(2):63-9. doi: 10.1016/j.kjms.2014.11.011. Epub 2014 Dec 17.
Eosinophils are important inflammatory cells involved in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). Vitamin D and its derivatives, in addition to their classic role as regulators of electrolytes homeostasis, have modulatory effects in immunological and inflammatory responses. Such properties suggest that vitamin D might also play a role in inflammatory airway diseases such as CRSwNP. In this study, we investigated the effect of vitamin D derivatives (calcitriol and tacalcitol) on the secretion of eotaxin and Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES), the two major eosinophil chemoattractants, in fibroblasts derived from the polyps of Taiwanese CRSwNP patients. Patients diagnosed with eosinophilic CRSwNP but without malignancies or asthma and undergoing elective endoscopic sinus surgery were recruited. Three primary fibroblast cultures were established using the polyp specimens obtained from these patients. The third to eighth passages of the fibroblasts were used for in vitro studies. Nasal polyp-derived fibroblasts were stimulated with IL-1β (10 ng/mL) for 24 hours, followed by replacement with media alone or with calcitriol or tacalcitol (10 μM) and incubation for another 24 hours. After the treatments, the levels of secreted eotaxin and RANTES were evaluated by ELISA assays. The results showed that IL-1β could substantially stimulate the secretion of eotaxin (p < 0.01) and RANTES (p < 0.01) in nasal polyp-derived fibroblasts. More importantly, this stimulatory effect was significantly suppressed by adding calcitriol (p ≤ 0.002 for eotaxin and p ≤ 0.008 for RANTES) or tacalcitol (p ≤ 0.009 for eotaxin and p ≤ 0.02 for RANTES). Therefore, the inhibitory effect of vitamin D derivatives on eotaxin and RANTES secretion might shed light not only on the disease mechanism, but also on the potential use of vitamin D in pharmacotherapy of Taiwanese patients with CRSwNP.
嗜酸性粒细胞是参与伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）发病机制的重要炎症细胞。维生素D及其衍生物，除了作为电解质稳态调节剂的经典作用外，在免疫和炎症反应中具有调节作用。这些特性表明维生素D可能在诸如CRSwNP等炎症性气道疾病中也发挥作用。在本研究中，我们调查了维生素D衍生物（骨化三醇和他卡西醇）对来自台湾CRSwNP患者息肉的成纤维细胞中嗜酸性粒细胞趋化因子和调节激活正常T细胞表达和分泌因子（RANTES）这两种主要嗜酸性粒细胞趋化剂分泌的影响。招募了被诊断为嗜酸性CRSwNP但无恶性肿瘤或哮喘且接受择期鼻内镜鼻窦手术的患者。使用从这些患者获得的息肉标本建立了三种原代成纤维细胞培养物。成纤维细胞的第三代至第八代用于体外研究。用白细胞介素-1β（10 ng/mL）刺激鼻息肉来源的成纤维细胞24小时，然后更换为单独的培养基或添加骨化三醇或他卡西醇（10 μM）并再孵育24小时。处理后，通过酶联免疫吸附测定法评估分泌的嗜酸性粒细胞趋化因子和RANTES的水平。结果表明，白细胞介素-1β可显著刺激鼻息肉来源的成纤维细胞中嗜酸性粒细胞趋化因子（p < 0.01）和RANTES（p < 0.01）的分泌。更重要的是，添加骨化三醇（嗜酸性粒细胞趋化因子p ≤ 0.002，RANTES p ≤ 0.008）或他卡西醇（嗜酸性粒细胞趋化因子p ≤ 0.009，RANTES p ≤ 0.02）可显著抑制这种刺激作用。因此，维生素D衍生物对嗜酸性粒细胞趋化因子和RANTES分泌的抑制作用不仅可能揭示疾病机制，还可能为台湾CRSwNP患者维生素D在药物治疗中的潜在应用提供线索。
