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

• Published in: BMB reports Vol. 50; no. 10; pp. 516 - 521
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society for Biochemistry and Molecular Biology 01.10.2017; 생화학분자생물학회
• Subjects: Bronchi - cytology; Bronchi - drug effects; Bronchi - metabolism; Cell Line; Claudin-1 - biosynthesis; Claudin-1 - genetics; Claudin-1 - metabolism; Down-Regulation - drug effects; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Gene Expression - drug effects; Humans; Inflammation - metabolism; Interleukin-6 - metabolism; Mucin 5AC - biosynthesis; Mucin 5AC - genetics; Mucin-1 - metabolism; Particulate Matter - toxicity; Reactive Oxygen Species - metabolism; Signal Transduction; Up-Regulation - drug effects; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/BMBRep.2017.50.10.100

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-acetylcysteine 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. [BMB Reports 2017; 50(10): 516-521].