Genkwadaphnin promotes leukocyte migration by increasing CD44 expression via PKD1/NF-κB signaling pathway

• Genkwadaphnin promotes leukocyte migration by increasing CD44 expression.
• GD-induced activation of PKD1/NF-κB signaling pathway is an essential mechanism for the regulation of CD44 expression in immune cells.
• GD might have a critical role in immune regulation through the increase of immune cell migration.

Genkwadaphnin (GD), an extract from the flower buds of Daphne genkwa Siebold & Zucc. (Thymelaeaceae) has been reported a significant anti-leukemic activity. However, its functional mechanism has not been defined well. To study the biological mechanism of GD function, we have investigated whether GD affects CD44 expression, which has a role in the regulation of immune cell motilities, and identified the related signaling pathways. GD treatment induced the increase of CD44 expression in a time- and concentration-dependent manner, which was specific for immune cells. GD activated PKD1/NF-κB signaling to induce CD44 expression, and resulted in the increased migration of K562 cells. In invasion assay, cell migratory ability was induced by GD and the transfection with CD44-specific short hairpin RNA resulted in reduction of its cell migration. GD treated human peripheral blood mononuclear cell (PBMC) were also shown the increased CD44 expression and migration. These data suggest that the induction of CD44 expression by GD treatment promotes immune cell transmigration resulting in the enhanced innate immunity.

Figure optionsDownload as PowerPoint slide