Dextromethorphan attenuates LPS-induced adhesion molecule expression in human endothelial cells

Area of Science:

• Endothelial cell biology
• Molecular immunology
• Pharmacology

Background:

• Lipopolysaccharide (LPS) stimulates inflammatory responses in endothelial cells.
• VCAM-1 and ICAM-1 are key cell adhesion molecules involved in inflammation.
• Human umbilical vein endothelial cells (HUVECs) are a model for studying endothelial function.

Purpose of the Study:

• To investigate the effect of Dextromethorphan (DXM) on VCAM-1 and ICAM-1 expression in LPS-stimulated HUVECs.
• To analyze the impact of DXM on monocyte adhesion and transmigration.
• To elucidate the signaling pathways affected by DXM in this inflammatory model.

Main Methods:

• HUVECs were treated with DXM and stimulated with LPS.
• Monocyte adhesion and transmigration assays were performed in vitro and ex vivo.
• Western blot and immunofluorescent staining were used to analyze signaling pathways, including ERK, Akt, and NF-κB.

Main Results:

• DXM inhibited LPS-induced THP-1 cell adhesion and transmigration.
• DXM significantly decreased LPS-induced expression of ICAM-1 and VCAM-1.
• DXM suppressed LPS-induced phosphorylation of ERK and Akt, Egr-1 translocation, IκBα degradation, and p65 nuclear translocation.

Conclusions:

• DXM inhibits endothelial cell adhesion by reducing ICAM-1 and VCAM-1 expression.
• The anti-inflammatory effects of DXM involve the suppression of ERK, Akt, and NF-κB signaling pathways.
• DXM demonstrates potential as an anti-inflammatory therapeutic agent, possibly modulating atherogenesis.