Fisetin Inhibits Lipopolysaccharide-Induced Macrophage Activation and Dendritic Cell Maturation

Abstract

Macrophages and dendritic cells are required for initiating innate immunity and adaptive immunity. Aberrant activation of macrophages and dendritic cells can cause detrimental immune responses; thus, agents effectively modulating their functions are of great clinical value. We herein investigated whether fisetin, a flavonoid prevalently present in fruits and vegetables, could inhibit macrophage activation and dendritic cell maturation. Fisetin suppressed LPS-induced NF-κB activation, expression of pro-inflammatory proteins (TNF-α and iNOS), MMP-9 activity, and phagocytic activity in macrophages. Furthermore, upon LPS-induced dendritic cell maturation, fisetin at nontoxic concentrations suppressed the expression of costimulatory molecules (CD80 and CD86), the production of cytokines (IL-12, IL-6, and TNF-α), and the endocytic activity of dendritic cells. Fisetin treatment significantly attenuated migration of dendritic cells into spleens and dendritic cell-mediated T cell activation in LPS-treated mice. Collectively, our data reveal that fisetin inhibits macrophage activation and impairs functional maturation of dendritic cells.