Department of Otolaryngology, Taizhou Central Hospital, Taizhou University, Taizhou 318000, China; Allergy Center, Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Department of Otolaryngology, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai 519000, China.
Allergy Center, Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Auris Nasus Larynx. 2020 Jun;47(3):401-409. doi: 10.1016/j.anl.2019.09.011. Epub 2019 Oct 19.
This study aimed to assess the possible role of hypoxia-inducible factor 1α (HIF-1α) in promoting neutrophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) patients.
We examined HIF-1α expression in sinonasal tissues from CRSwNP patients and healthy controls by using immunohistochemistry, qRT-PCR, and western blot. Next, the stimulatory effects of several cytokines (IFN-γ, IL-17A, IL-6, etc.) and reagents (dexamethasone (DEX), clarithromycin (CAM) and curcumin (CUM)) on HIF-1α expression in cultured normal nasal epithelial cells (NECs) were also evaluated. Moreover, the effects of CAM and glucocorticoid on nasal symptoms and signs of uncontrolled neutrophilic CRSwNP patients were evaluated.
The mRNA and protein expression of HIF-1α were significantly increased in polyp tissues compared with healthy controls (P < 0.05), and the HIF-1α level in polyp tissues was positively associated with IL-17A production and tissue neutrophilia (P < 0.05). Moreover, in cultured NECs, HIF-1α expression was upregulated in the presence of IL-17A and IL-6 (P < 0.05). Both CAM and CUM showed an additive effect with DEX in inhibiting HIF-1α expression (P < 0.05). Moreover, combined glucocorticoid and CAM significantly improved nasal symptoms and signs compared with glucocorticoid alone in uncontrolled neutrophilic CRSwNP patients (P < 0.05).
Our findings indicate that HIF-1α is associated with neutrophilic inflammation and glucocorticoid resistance in CRSwNP patients.
本研究旨在评估缺氧诱导因子 1α（HIF-1α）在促进慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）患者中性粒细胞炎症中的可能作用。
我们通过免疫组织化学、qRT-PCR 和 Western blot 检测了 CRSwNP 患者和健康对照者鼻组织中的 HIF-1α 表达。接下来，还评估了几种细胞因子（IFN-γ、IL-17A、IL-6 等）和试剂（地塞米松（DEX）、克拉霉素（CAM）和姜黄素（CUM））对培养的正常鼻上皮细胞（NEC）中 HIF-1α 表达的刺激作用。此外，还评估了 CAM 和糖皮质激素对未经控制的中性粒细胞 CRSwNP 患者鼻部症状和体征的影响。
与健康对照组相比，息肉组织中 HIF-1α 的 mRNA 和蛋白表达均显著增加（P<0.05），且息肉组织中 HIF-1α 水平与 IL-17A 产生和组织中性粒细胞增多呈正相关（P<0.05）。此外，在培养的 NEC 中，存在 IL-17A 和 IL-6 时 HIF-1α 表达上调（P<0.05）。CAM 和 CUM 与 DEX 联合使用均可抑制 HIF-1α 表达（P<0.05）。此外，与单独使用糖皮质激素相比，糖皮质激素和 CAM 联合使用可显著改善未经控制的中性粒细胞 CRSwNP 患者的鼻部症状和体征（P<0.05）。
我们的研究结果表明，HIF-1α 与 CRSwNP 患者的中性粒细胞炎症和糖皮质激素抵抗有关。
