The PI3K-Akt-HIF-1α Pathway Reducing Nasal Airway Inflammation and Remodeling in Nasal Polyposis

Abstract

Objective: Previous studies suggested that hypoxia-inducible factor-1α (HIF-1α) plays an important role in the progression of inflammation and remodeling of chronic rhinosinusitis with nasal polyposis. However, the molecule mechanisms of HIF-1α activation and regulation of cytokine expressions, such as interleukin (IL) 25 and IL-17RB, in nasal polyposis are not clear. Method: The IL-25 and IL-17RB levels in human nasal epithelial cells after stimulation by lipopolysaccharide (LPS) were detected by enzyme-linked immunosorbent assay method, and the proteins of HIF-1α and p-Akt were detected by Western blot method. Moreover, we evaluated the cytokine levels in the nasal mucosa of a murine model of nasal polyposis. Results: The levels of IL-25 and IL-17RB showed dose- and time-dependent release in response to LPS stimulation. The proteins of HIF-1α and p-Akt were both increased significantly after LPS stimulation. After inhibition of PI3K/Akt pathway by PI3K inhibitor LY294002, the levels of IL-25 and IL-17RB and HIF-1α were decreased by LPS stimulation. Conclusions: Inhibition of PI3K or HIF-1α pathway could significantly reduce growth factor production and decrease nasal inflammation. The HIF-1α pathway could be a novel therapeutic approach for reducing nasal airway inflammation and remodeling in nasal polyposis.