Zhijian Yu1, Yu Wang2, Xianting Hu3, Hangyu Xu4, Miaomiao Han3, Jia Zhang5, Weiping Wen4, Hairong Shu6, Huabin Li7. 1. 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. 2. Allergy Center, Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China. 3. Department of Otolaryngology, Head and Neck Surgery, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai 200031, China. 4. Department of Otolaryngology, Taizhou Central Hospital, Taizhou University, Taizhou 318000, China. 5. Allergy Center, Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Department of Otolaryngology, Head and Neck Surgery, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai 200031, China. 6. Department of Otolaryngology, Taizhou Central Hospital, Taizhou University, Taizhou 318000, China. Electronic address: drshu@126.com. 7. 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. Electronic address: allergyli@163.com.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Our findings indicate that HIF-1α is associated with neutrophilic inflammation and glucocorticoid resistance in CRSwNP patients.
OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Our findings indicate that HIF-1α is associated with neutrophilic inflammation and glucocorticoid resistance in CRSwNP patients.