Abstract：
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with aberrant host defense responses. However, whether innate immunity is similarly impaired in patients with eosinophilic and those with noneosinophilic CRSwNP remains unclear.
OBJECTIVE: We sought to evaluate the expression and possible modulation of short palate, lung, and nasal epithelium clone 1 (SPLUNC1), an innate immune molecule, in the 2 CRSwNP subsets.
METHODS: Polyp tissue and uncinate processes were collected from 40 patients with CRSwNP, 27 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 22 control subjects. Expression of SPLUNC1; Toll-like receptor (TLR) 2, TLR3, and TLR4; and the proinflammatory cytokines IL-1α, IL-4, IL-13, IL-17A, and IFN-γ was examined in nasal tissues. Additionally, SPLUNC1 expression in response to specific inflammatory stimulation was measured in cultured polyp epithelial cells and A549 cells.
RESULTS: Polyp tissues exhibited significantly decreased expression of SPLUNC1 and other innate immune molecules compared with uncinate process tissues from patients with CRSwNP (P < .05), patients with CRSsNP, and healthy control subjects. Moreover, the eosinophilic CRSwNP subset exhibited significantly decreased SPLUNC1 expression and numbers of submucosal glands, as well as significantly increased IL-4 and IL-13 mRNA levels, compared with the noneosinophilic subset (P < .05). Accordingly, SPLUNC1 expression in polyp epithelial cells was significantly inhibited by IL-4 and IL-13 stimulation in vitro but was significantly upregulated after stimulation with TLR agonists and glucocorticoids (P < .05).
CONCLUSIONS: Differential SPLUNC1 suppression between the eosinophilic and noneosinophilic CRSwNP subsets suggests that they possess distinct pathogenic mechanisms. This finding might benefit the design of appropriate therapeutic interventions targeted to each subset.
OBJECTIVE: We sought to evaluate the expression and possible modulation of short palate, lung, and nasal epithelium clone 1 (SPLUNC1), an innate immune molecule, in the 2 CRSwNP subsets.
METHODS: Polyp tissue and uncinate processes were collected from 40 patients with CRSwNP, 27 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 22 control subjects. Expression of SPLUNC1; Toll-like receptor (TLR) 2, TLR3, and TLR4; and the proinflammatory cytokines IL-1α, IL-4, IL-13, IL-17A, and IFN-γ was examined in nasal tissues. Additionally, SPLUNC1 expression in response to specific inflammatory stimulation was measured in cultured polyp epithelial cells and A549 cells.
RESULTS: Polyp tissues exhibited significantly decreased expression of SPLUNC1 and other innate immune molecules compared with uncinate process tissues from patients with CRSwNP (P < .05), patients with CRSsNP, and healthy control subjects. Moreover, the eosinophilic CRSwNP subset exhibited significantly decreased SPLUNC1 expression and numbers of submucosal glands, as well as significantly increased IL-4 and IL-13 mRNA levels, compared with the noneosinophilic subset (P < .05). Accordingly, SPLUNC1 expression in polyp epithelial cells was significantly inhibited by IL-4 and IL-13 stimulation in vitro but was significantly upregulated after stimulation with TLR agonists and glucocorticoids (P < .05).
CONCLUSIONS: Differential SPLUNC1 suppression between the eosinophilic and noneosinophilic CRSwNP subsets suggests that they possess distinct pathogenic mechanisms. This finding might benefit the design of appropriate therapeutic interventions targeted to each subset.
摘要：
背景：慢性鼻窦炎伴鼻息肉（CRSwNP）是一种高度异质性的疾病，具有异常的宿主防御反应。然而,嗜酸性粒细胞性和非嗜酸性粒细胞性CRSwNP患者的先天免疫是否也有类似的损害尚不清楚.
目的：我们试图评估短腭的表达和可能的调节，肺，和鼻上皮克隆1（SPLUNC1），一种先天免疫分子，在2个CRSwNP子集中。
方法：收集40例CRSwNP患者的息肉组织和钩突，27例慢性鼻-鼻窦炎无鼻息肉（CRSsNP），和22个对照对象。SPLUNC1、Toll样受体(TLR)2、TLR3和TLR4及促炎细胞因子IL-1α的表达,IL-4,IL-13,IL-17A,在鼻组织中检测IFN-γ。此外,在培养的息肉上皮细胞和A549细胞中测量响应于特异性炎症刺激的SPLUNC1表达。
结果：与CRSwNP患者的钩突组织相比，息肉组织显示SPLUNC1和其他先天免疫分子的表达显着降低（P<0.05），CRSsNP患者，和健康的对照受试者。此外，嗜酸性粒细胞CRSwNP亚群表现出显著降低的SPLUNC1表达和粘膜下腺数量,以及显著增加IL-4和IL-13mRNA水平，与非嗜酸性粒细胞亚群相比（P<0.05）。因此，在体外IL-4和IL-13刺激下，息肉上皮细胞中SPLUNC1的表达受到显着抑制，但在TLR激动剂和糖皮质激素刺激后，SPLUNC1的表达显着上调（P<0.05）。
结论：嗜酸性粒细胞和非嗜酸性粒细胞CRSwNP亚群之间的SPLUNC1抑制差异表明它们具有不同的致病机制。这一发现可能有利于设计针对每个子集的适当治疗干预措施。
目的：我们试图评估短腭的表达和可能的调节，肺，和鼻上皮克隆1（SPLUNC1），一种先天免疫分子，在2个CRSwNP子集中。
方法：收集40例CRSwNP患者的息肉组织和钩突，27例慢性鼻-鼻窦炎无鼻息肉（CRSsNP），和22个对照对象。SPLUNC1、Toll样受体(TLR)2、TLR3和TLR4及促炎细胞因子IL-1α的表达,IL-4,IL-13,IL-17A,在鼻组织中检测IFN-γ。此外,在培养的息肉上皮细胞和A549细胞中测量响应于特异性炎症刺激的SPLUNC1表达。
结果：与CRSwNP患者的钩突组织相比，息肉组织显示SPLUNC1和其他先天免疫分子的表达显着降低（P<0.05），CRSsNP患者，和健康的对照受试者。此外，嗜酸性粒细胞CRSwNP亚群表现出显著降低的SPLUNC1表达和粘膜下腺数量,以及显著增加IL-4和IL-13mRNA水平，与非嗜酸性粒细胞亚群相比（P<0.05）。因此，在体外IL-4和IL-13刺激下，息肉上皮细胞中SPLUNC1的表达受到显着抑制，但在TLR激动剂和糖皮质激素刺激后，SPLUNC1的表达显着上调（P<0.05）。
结论：嗜酸性粒细胞和非嗜酸性粒细胞CRSwNP亚群之间的SPLUNC1抑制差异表明它们具有不同的致病机制。这一发现可能有利于设计针对每个子集的适当治疗干预措施。
