title: Ambroxol inhibits platelet-derived growth factor production in human monocytic cells.
abstract: Several growth factors, including platelet-derived growth factor (PDGF), have been implicated in the mechanism of lung and airway remodeling. We investigated the effect of ambroxol, trans-4-[(2-amino-3,5-dibromobenzyl) amino] cyclohexanol hydrochloride, on the lipopolysaccharide-induced PDGF production in human monocytic cells, THP-1. Ambroxol inhibited the lipopolysaccharide-induced PDGF-AB production via PDGF-A mRNA expression. Lipopolysaccharide activated p44/42 extracellular signal-regulated kinase (ERK), and ambroxol attenuated the lipopolysaccharide-induced p44/42 ERK activation. Furthermore, mitogen-activated protein kinase kinase (MEK)-1-specific inhibitor, 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD 98059), blocked the lipopolysaccharide-induced p44/42 ERK activation and PDGF production. These findings indicate that ambroxol inhibits the lipopolysaccharide-induced PDGF production due to the suppression of p44/42 ERK activity.
authors.affiliation: First Department of Internal Medicine, Gunma University Faculty of Medicine, School of Medicine, 3-39-15 Showa-machi, Gunma, 371-8511, Maebashi, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Utsugi
authors.forename: Kunio
authors.initials: K
authors.lastname: Dobashi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Koga
authors.forename: Ken
authors.initials: K
authors.lastname: Masubuchi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Endou
authors.forename: Tsugio
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
mesh_terms: D000551:Ambroxol / Q000494:pharmacology*; D002460:Cell Line; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000187:drug effects* / Q000378:metabolism
chemical_list: D005419:Flavonoids; D008070:Lipopolysaccharides; D010982:Platelet-Derived Growth Factor; D000551:Ambroxol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one