Ambroxol inhibits platelet-derived growth factor production in human monocytic cells

Eur J Pharmacol. 2002 Feb 1;436(1-2):47-51. doi: 10.1016/s0014-2999(01)01609-0.

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.

MeSH terms

  • Ambroxol / pharmacology*
  • Cell Line
  • Flavonoids / pharmacology
  • Humans
  • Lipopolysaccharides / pharmacology
  • Mitogen-Activated Protein Kinase 1 / drug effects
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • Monocytes / cytology
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Platelet-Derived Growth Factor / drug effects*
  • Platelet-Derived Growth Factor / metabolism

Substances

  • Flavonoids
  • Lipopolysaccharides
  • Platelet-Derived Growth Factor
  • Ambroxol
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one