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Original Article

Korean J Physiol Pharmacol 2020; 24(2): 157-163

Published online March 1, 2020 https://doi.org/10.4196/kjpp.2020.24.2.157

Copyright © The Korean Journal of Physiology & Pharmacology.

Eupatilin downregulates phorbol 12‐myristate 13‐acetate-induced MUC5AC expression via inhibition of p38/ERK/JNK MAPKs signal pathway in human airway epithelial cells

Yoon-Hee Cheon1, Min Seob Kim2, Ju-Young Kim3, Dong Hyun Kim4, Seung Yoon Han4, and Jae-Hoon Lee4,*

1Center for Core Research Facilities, Wonkwang University School of Medicine, 2Department of Physiology, Wonkwang University School of Medicine, 3Medical Convergence Research Center, Wonkwang University Hospital, 4Department of Otolaryngology, Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, Iksan 54538, Korea

Correspondence to:*Jae-Hoon Lee
E-mail: Leejaehoon64@gmail.com

Received: August 16, 2019; Revised: January 18, 2020; Accepted: January 21, 2020

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Chronic inflammatory airway diseases, such as chronic rhinosinusitis, chronic obstructive pulmonary disease, and asthma, are associated with excessive mucus production. Hence, the regulation of mucus production is important for the treatment of upper and lower airway diseases. Eupatilin is a pharmacologically active ingredient obtained from Artemisia asiatica Nakai (Asteraceae) and exerts potent anti-inflammatory, anti-allergic, and anti-tumor activities. In the present study, we investigated the effect of eupatilin on phorbol 12‐myristate 13‐acetate (PMA)-induced MUC5AC and MUC5B expression in human airway epithelial cells. We found that eupatilin treatment significantly inhibited PMA-induced mucus secretion in PAS staining. In addition, qRT-PCR results showed that eupatilin dose-dependently decreased the mRNA expression of MUC5AC in human airway epithelial cells. Western blot and immunofluorescence assay also showed that PMA-induced protein expression of MUC5AC was inhibited by eupatilin treatment. Finally, we investigated MAPKs activity after stimulation with PMA using western blot analysis in human airway epithelial cells. The results showed that eupatilin downregulated the levels of phosphorylated p38, ERK, and JNK. In summary, the anti-inflammatory activities of eupatilin, characterized as the suppression of MUC5AC expression and secretion in human airway epithelial cells, were found to be associated with the inhibition of p38/ERK/JNK MAPKs signaling pathway of MUC5AC secretion.

Keywords: Eupatilin, MAPKs, MUC5AC, Periodic acid Schiff’s staining, Phorbol 12‐myristate 13‐acetate