title: Inhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorum root-derived saponin in A549 cells.
abstract: Mucin overproduction is a hallmark of chronic airway diseases such as chronic obstructive pulmonary disease. In this study, we investigated the inhibition of acrolein-induced expression of mucin 5, subtypes A and C (MUC5AC) by Changkil saponin (CKS) in A549 cells. Acrolein, a known toxin in tobacco smoke and an endogenous mediator of oxidative stress, increases the expression of airway MUC5AC, a major component of airway mucus. CKS, a Platycodon grandiflorum root-derived saponin, inhibited acrolein-induced MUC5AC expression and activity, through the suppression of NF-κB activation. CKS also repressed acrolein-induced phosphorylation of ERK1/2, JNK1/2, and p38MAPK, which are upstream signaling molecules that control MUC5AC expression. In addition, the MAPK inhibitors PD98059 (ERK1/2), SP600125 (JNK1/2), and SB203580 (p38 MAPK), and a PKC delta inhibitor (rottlerin; PKCδ) inhibited acrolein-induced MUC5AC expression and activity. CKS repressed acrolein-induced phosphorylation of PKCδ. Moreover, a reactive oxygen species (ROS) inhibitor, N-acetylcysteine, inhibited acrolein-induced MUC5AC expression and activity through the suppression of PKCδ and MAPK activation, and CKS repressed acrolein-induced ROS production. These results suggest that CKS suppresses acrolein-induced MUC5AC expression by inhibiting the activation of NF-κB via ROS-PKCδ-MAPK signaling.
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, 220 Gung-dong, Daejeon 305-764, Republic of Korea.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Yong Pil
authors.initials: YP
authors.lastname: Hwang
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Han
authors.forename: Hyung Gyun
authors.initials: HG
authors.lastname: Kim
authors.forename: Bong Hwan
authors.initials: BH
authors.lastname: Park
authors.forename: Hyun Sun
authors.initials: HS
authors.lastname: Lee
authors.forename: Byung Keun
authors.initials: BK
authors.lastname: Park
authors.forename: Young Chun
authors.initials: YC
authors.lastname: Lee
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Chung
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
mesh_terms: D000171:Acrolein / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D018517:Plant Roots / Q000737:chemistry*; D031238:Platycodon / Q000737:chemistry*; D011494:Protein Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D017382:Reactive Oxygen Species; D012503:Saponins; D000171:Acrolein; D011494:Protein Kinases