title: The inhibition of aldose reductase on mucus production induced by interleukin-13 in the human bronchial epithelial cells.
abstract: 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 2h. 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.
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
authors.forename: Depeng
authors.initials: D
authors.lastname: Jiang
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Victor P
authors.initials: VP
authors.lastname: Kolosov
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052160:Benzothiazoles / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010793:Phthalazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism
chemical_list: D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D018793:Interleukin-13; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D016328:NF-kappa B; D010793:Phthalazines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; C067172:zopolrestat; D000449:Aldehyde Reductase; C507924:JAK2 protein, human; D053614:Janus Kinase 2