Natural polyamine inhibits mouse skin inflammation and macrophage activation

Abstract

Natural polyamines are some of the most abundant polycationic molecules in eukaryotic cells, regulating gene expression. Polyamines have been reported to possess anti-inflammatory activities in many model inflammation systems. However, there is no report on their role in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dermal edema. Mouse ear edema was induced by TPA. Edema biopsies were investigated using H&E staining. Levels of nitric oxide (NO) were determined using the Griess reaction. Tumor necrosis factor α (TNFα) and interleukin (IL)-1β levels in cell supernatants were measured by TNFα and IL-1β ELISA kits. Spermidine and spermine caused significant decreases in ear thickness, water content, and neutrophil infiltrations in comparison with negative control (p < 0.05). External polyamines reduced the levels of inflammatory mediators such as NO, TNFα, and IL-1β in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. Spermine had a higher inhibitory effect on the production of cytokines such as IL-1β and TNFα in LPS-stimulated murine macrophages compared to other polyamines. Our findings clearly demonstrated that polyamines are involved in the anti-inflammatory effect by reducing dermal edema thickness and other inflammatory mediators like NO and cytokines in a dose-dependent manner.