IL-13 May Could Enhance the Proliferation and Affect the Differentiation of Nasal Epithelium Basal Cells Through the mTOR/p70S6K1 Pathway in Chronic Rhinosinusitis With Nasal Polyps.

Abstract

Background: One of the hallmarks of Chronic rhinosinusitis with nasal polyps (CRSwNP) is the overexpression of IL-13, which may influence the proliferation and differentiation of nasal epithelial basal cells. However, the pathway is not clear enough, and the mTOR/p70S6K1 pathway is related to cell growth. This study was trying to explore if IL-13 could impact nasal epithelial basal cells through the mTOR/p70S6K1 pathway. Methods: PCR, western blot (WB), and immunohistochemistry (IHC) were used to compare the difference between IL-13 and the mTOR/p70S6K1 pathway-related molecules expression level between the healthy control (HC) and CRSwNP groups. WB, 5-ethynyl-2'-deoxyuridine staining, and Immunofluorescent (IF) were performed on human nasal epithelial progenitor cells (HNEPCs) to detect the proliferation ability under the effect of IL-13. In addition, qRT-PCR, WB, and IF were used to detect the differentiation ability with the stimulation of IL-13 in the air-liquid interface (ALI) system. Results: The expression of IL-13, mTOR/p70S6K1-related molecules, and proliferation-related molecules Ki67, CDK2, and cyclin E1 were upregulated in CRSwNP compared to HC. In HNEPCs, IL-13 could stimulate nasal epithelial cells proliferating through the mTOR/p70S6K1 pathway, and this phenomenon could be inhibited when mTOR (with rapamycin) and S6K1 (with PF-4708671) were blocked. In the ALI system, the effect of IL-13 added in the proliferation phase could persist in the proliferation and differentiation stage, affecting the nasal epithelial progenitor/stem cells' irregular differentiation. Conclusion: IL-13 may affect the proliferation and differentiation of nasal epithelial progenitor/stem cells through the mTOR/p70S6K1 pathway, which may affect the development of nasal polyps.