The inhibition of aldose reductase on mucus production induced by interleukin-13 in the human bronchial epithelial cells

This study investigated whether aldose reductase (AR) inhibition affects interleukin (IL)-13-induced mucus production in the human bronchial epithelial cell line-16 (HBE16) cells. The HBE16 cells were cultured with AR inhibitors (zopolrestat) or were transfected with an AR small interfering (si)RNA. Subsequently, the cells were stimulated with 10 ng/ml IL-13 for 2 h. The levels of mucin (MUC)5AC mRNA and protein were measured by using RT-PCR or ELISA. Intracellular reactive oxygen species (ROS) were measured fluorimetrically with the CM-H2DCFDA probe. Western blotting was performed to determine the levels of AR, phosphorylated signal transducer and activator of transcription 6 (p-STAT6) and phosphorylated Janus kinase 2 (p-JAK2). The results show that treatment with zopolrestat or transfection with AR siRNA significantly suppressed IL-13-stimulated MUC5AC mRNA and protein in the HBE16 cells (P < 0.05). AR inhibition could suppress IL-13-induced ROS generation, the phosphorylation of JAK2/STAT6 pathway and the activation of nuclear factor (NF)-kappa B, thereby decreasing mucus production in vitro (all P < 0.05). Therefore, the inhibition of AR could be a therapeutic target for mucus hypersecretion in chronic inflammation lung disease.

► We investigate the effects of aldose reductase (AR) inhibition on mucus production and the possible mechanism. ► AR inhibition could reduce MUC5AC mRNA and protein expression induced by IL-13 in the HBE16 cells. ► AR inhibition could block IL-13-stimulated ROS generation. ► The activation of JAK2, STAT6 and NF-kappa B was suppressed after treatment with zopolrestat or transfection with AR siRNA.