Interleukin-17A Promotes MUC5AC Expression and Goblet Cell Hyperplasia in Nasal Polyps via the Act1-Mediated Pathway

Abstract

BackgroundRecent studies demonstrated that nasal polyps (NP) patients in China and other Asian regions possessed distinct Th17-dominant inflammation and enhanced tissue remodeling. However, the mechanism underlying these observations is not fully understood. This study sought to evaluate the association of interleukin (IL)-17A with MUC5AC expression and goblet cell hyperplasia in Chinese NP patients and to characterize the signaling pathway underlying IL-17A-induced MUC5AC expression in vitro.MethodWe enrolled 25 NP patients and 22 normal controls and examined the expression of IL-17A, MUC5AC and act1 in polyp tissues by immunohistochemical (IHC) staining, quantitative polymerase chain reaction (qPCR) and western blot. Moreover, by using an in vitro culture system of polyp epithelial cells (PECs), IL-17A-induced gene expression was screened in cultured PECs by DNA microarray. The expression of IL-17RA, IL-17RC, act1 and MUC5AC and the activation of the MAPK pathway (ERK, p38 and JNK), were further examined in cultured PECs and NCI-H292 cells by qPCR and western blotting, respectively.ResultsWe found that increased IL-17A production was significantly correlated with MUC5AC and act1 expression and goblet cell hyperplasia in polyp tissues (p<0.05). IL-17A significantly stimulated the expression of IL-17RA, IL-17RC, act1 and MUC5AC, and the activation of the MAPK pathway in cultured PECs and NCI-H292 cells (p<0.05). In addition, IL-17RA, IL-17RC and act1 siRNA significantly blocked IL-17A-induced MUC5AC production in vitro (p<0.05).ConclusionOur results suggest that IL-17A plays a crucial role in stimulating the production of MUC5AC and goblet cell hyperplasia through the act1-mediated signaling pathway and may suggest a promising strategy for the management of Th17-dominant NP patients.

Enhanced expression of SAM-pointed domain-containing Ets-like factor in Chronic rhinosinusitis with nasal polyps

“…The molecular mechanisms underlying neutrophilic cytokine‐induced MUC5AC remain largely unknown. Previously, we reported that IL‐17A is able to promote MUC5AC production and goblet cell hyperplasia via an act1‐dependent manner . In the present study, we further evaluated the regulatory effect of SPDEF on MUC5AC expression in cytokine‐induced airway epithelial cells.…”

Lentiviral shRNA against KCa3.1 inhibits allergic response in allergic rhinitis and suppresses mast cell activity via PI3K/AKT signaling pathway

“…To further illuminate the roles of LV-KCa3.1-shRNA on goblet cell and mast cell in AR mice, mRNA levels of KCa3.1, MUC5AC, which is mainly secreted by goblet cell 20 , and tryptase, known as a key mast cell marker which mainly exists in the secretory granules of mast cell 21 , were assayed by real-time PCR.…”

A Retrospective Analysis of &#x03B3;δ T Cell Expression in Chronic Rhinosinusitis and Its Association with Recurrence of Nasal Polyps

“…The expression of IL-17 has been reported to be increased in the nasal mucosa of CRSwNP patients and is closely related to the infiltration of eosinophils and neutrophils [47,48,49]. Recently, Xia et al [50] reported that IL-17A plays a crucial role in stimulating the production of MUC5AC and goblet cell hyperplasia through the act1-mediated signalling pathway in CRSwNP patients in China. But the origin of cell-secreted IL-17 in nasal mucosa of CRS patients remains unclear.…”