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Ambroxol inhibits platelet-derived growth factor production in human monocytic cells
Mitsuyoshi Utsugi1, Kunio Dobashi, Yasuhiko Koga
1First Department of Internal Medicine, Gunma University Faculty of Medicine, School of Medicine, 3-39-15 Showa-machi, Gunma, 371-8511, Maebashi, Japan.
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.
Insights
Ambroxol effectively reduces lipopolysaccharide-induced platelet-derived growth factor (PDGF) production in human cells. This inhibition occurs by suppressing the p44/42 extracellular signal-regulated kinase (ERK) pathway, a key factor in airway remodeling.
Area of Science:
- Cell Biology
- Molecular Biology
- Pharmacology
Background:
- Platelet-derived growth factor (PDGF) plays a role in lung and airway remodeling.
- Lipopolysaccharide (LPS) is known to induce PDGF production.
Purpose of the Study:
- To investigate the effect of ambroxol on LPS-induced PDGF production in human monocytic cells (THP-1).
- To elucidate the underlying molecular mechanism, specifically the involvement of the p44/42 extracellular signal-regulated kinase (ERK) pathway.
Main Methods:
- Human monocytic cells (THP-1) were treated with lipopolysaccharide (LPS) and ambroxol.
- Platelet-derived growth factor (PDGF)-AB production and PDGF-A mRNA expression were measured.
- Activation of p44/42 extracellular signal-regulated kinase (ERK) was assessed.
- The effect of a MEK-1 inhibitor (PD 98059) on LPS-induced PDGF production and ERK activation was evaluated.
Main Results:
- Ambroxol significantly inhibited LPS-induced PDGF-AB production by suppressing PDGF-A mRNA expression.
- LPS treatment activated p44/42 ERK, an effect attenuated by ambroxol.
- The MEK-1 inhibitor PD 98059 blocked both LPS-induced p44/42 ERK activation and PDGF production.
Conclusions:
- Ambroxol inhibits lipopolysaccharide-induced PDGF production in human monocytic cells.
- This inhibitory effect is mediated through the suppression of p44/42 ERK pathway activation.
- Ambroxol may represent a therapeutic agent for conditions involving PDGF-mediated airway remodeling.