Asian Sand Dust Regulates IL-32 Production in Airway Epithelial Cells: Inhibitory Effect of Glucocorticoids

Abstract

Purpose

Epidemiologic studies have reported that Asian sand dust (ASD) is associated with chronic inflammatory diseases of the respiratory system. Glucocorticoids (GCs) have potent anti-inflammatory properties. The aims of this study were to evaluate the effects of GCs on ASD-induced interleukin-32 (IL-32) expression and to identify the underlying signaling pathways in airway epithelial cells.

Methods

A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate cytotoxicity in A549 and human primary nasal epithelial cells. Expression levels of IL-32 messenger RNA and protein were measured by Western blot, real-time polymerase chain reaction, ELISA, and immunofluorescence staining. Signaling pathways were analyzed using specific inhibitors of Akt, MAPK, or NF-κB. The effects of GCs on the expression of ASD-induced IL-32 were confirmed with ex vivo organ cultures of the nasal interior turbinate.

Results

ASD (0–400 ng/mL) had no significant cytotoxic effects in A549 cells and human primary nasal epithelial cells. Expression levels of IL-32 were dose-dependently upregulated by ASD treatment in A549 cells. ASD induced phosphorylation of Akt, MAPK, and NF-κB, whereas GCs and specific inhibitors of Akt, MAPK, and NF-κB downregulated these activations and the expression of IL-32. These findings were further confirmed in human primary nasal epithelial cells and ex vivo organ cultures of the nasal interior turbinate.

Conclusions

GCs have an inhibitory effect on ASD-induced IL-32 expression via the Akt, MAPK, and NF-κB signaling pathways in airway epithelial cells.