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

  • Kim, Sang-Su (Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine) ;
  • Kim, Cheol Hong (Department of Pediatrics, Sungkyunkwan University Samsung Changwon Hospital) ;
  • Kim, Ji Wook (Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine) ;
  • Kung, Hsi Chiang (Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine) ;
  • Park, Tae Woo (Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine) ;
  • Shin, Yu Som (Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine) ;
  • Kim, Ju Deok (Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine) ;
  • Ryu, Siejeong (Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine) ;
  • Kim, Wang-Joon (Department of Physiology, Kosin University College of Medicine) ;
  • Choi, Yung Hyun (Department of Biochemistry, College of Korean Medicine, Dong-Eui University) ;
  • Song, Kyoung Seob (Department of Physiology, Kosin University College of Medicine)
  • Received : 2017.06.14
  • Accepted : 2017.09.05
  • Published : 2017.10.31

Abstract

$CLB_{2.0}$, a constituent of PM, induces secretion of multiple cytokines and chemokines that regulate airway inflammation. Specifically, IL-6 upregulates $CLB_{2.0}$-induced MUC5AC and MUC1 expression. Interestingly, of the tight junction proteins examined, claudin-1 expression was inhibited by $CLB_{2.0}$. While the overexpression of claudin-1 decreased $CLB_{2.0}$-induced MUC5AC expression, it increased the expression of the anti-inflammatory mucin, MUC1. $CLB_{2.0}$-induced IL-6 secretion was mediated by ROS. The ROS scavenger N-acetyl-cysteine inhibited $CLB_{2.0}$-induced IL-6 secretion, thereby decreasing the $CLB_{2.0}$-induced MUC5AC expression, whereas $CLB_{2.0}$-induced MUC1 expression increased. $CLB_{2.0}$ activated the ERK1/2 MAPK via a ROS-dependent pathway. ERK1/2 downregulated the claudin-1 and MUC1 expressions, whereas it dramatically increased $CLB_{2.0}$-induced MUC5AC expression. These findings suggest that $CLB_{2.0}$-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 $CLB_{2.0}$-induced MUC5AC and MUC1 expression via ROS-mediated downregulation of claudin-1 expression to maintain mucus homeostasis in the airway.

Keywords

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

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

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