Airborne particulate matter increases MUC5AC expression by downregulating Claudin-1 expression in human airway cells

作者：Kim Sang Su; Kim Cheol Hong; Kim Ji Wook; Kung Hsi Chiang; Park Tae Woo; Shin Yu Som; Kim Ju Deok; Ryu Siejeong; Kim Wang Joon; Choi Yung Hyun; Song Kyoung Seob^*

来源：BMB Reports, 2017, 50(10): 516-521.

DOI：10.5483/BMBRep.2017.50.10.100

• Airway inflammation
• Claudin-1
• IL-6
• MUC1
• MUC5AC
• PM

CLB2.0, a constituent of PM, induces secretion of multiple cytokines and chemokines that regulate airway inflammation. Specifically, IL-6 upregulates CLB2.0-induced MUC5AC and MUC1 expression. Interestingly, of the tight junction proteins examined, claudin-1 expression was inhibited by CLB2.0 While the overexpression of claudin-1 decreased CLB2.0-induced MUC5AC expression, it increased the expression of the anti-inflammatory mucin, MUC1. CLB2.0-induced IL-6 secretion was mediated by ROS. The ROS scavenger N-acetyl-cysteine inhibited CLB2.0-induced IL-6 secretion, thereby decreasing the CLB2.0-induced MUC5AC expression, whereas CLB2.0-induced MUC1 expression increased. CLB2.0 activated the ERK1/2 MAPK via a ROS-dependent pathway. ERK1/2 downregulated the claudin-1 and MUC1 expressions, whereas it dramatically increased CLB2.0-induced MUC5AC expression. These findings suggest that CLB2.0-induced ERK1/2 activation acts as a switch for regulating inflammatory conditions though a ROS-dependent pathway. Our data also suggest that secreted IL-6 regulates CLB2.0-induced MUC5AC and MUC1 expression via ROS-mediated downregulation of claudin-1 expression to maintain mucus homeostasis in the airway.

• 出版日期2017
• 单位河北医科大学