Natural polyamine inhibits mouse skin inflammation and macrophage activation

Objective: 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. Methods: 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. Results: 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. Conclusion: 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.