Overexpression of hypoxia-inducible factor 1α is associated with neutrophilic inflammation in chronic rhinosinusitis with nasal polyps.

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.