FP03 Niacinamide decreases the inflammatory response of macrophages and enhances the survival of ultraviolet radiation-exposed macrophages
Danielle Tan, Rajia Bahri, Sebastien Viatte, Victoria L Newton, Silvia Bulfone-PausAbstract
Introduction and aims
Skin-resident macrophages are strongly influenced by ultraviolet (UV) radiation (UVR). Hence, this study investigates how niacinamide, a vitamin B3 derivative with anti-inflammatory properties widely used in skincare, influences their differentiation, polarization and inflammatory responses [reactive oxygen species (ROS) production, caspase-1 activity, and cytokine release] with or without UVR exposure.
Methods
THP-1-derived macrophages were used as a model for skin-resident macrophages to study the effects of direct UVR and indirect exposure via UV-irradiated keratinocyte supernatant. Niacinamide was tested on M0, M1 and M2 macrophages with or without UVR or supernatant treatment at 24 and/or 48 h for its impact on cell viability (Annexin V, 7AAD, LiveDead), macrophage differentiation/polarization [CD11b(M0), CD169(activation), CD80(M1), HLA-DR(M1), CD200R(M2)] and cytokine release [interleukin (IL)-8, IL-6, IL-1β, tumour necrosis factor (TNF)-α, IL-10] by flow cytometry. ROS and caspase-1 activity were measured in M0, M1, and M2 macrophages using commercial fluorescence- and luminescence-based assays, respectively.
Results
Niacinamide significantly mitigated UVR-induced apoptosis and necrosis in M0 THP-1 cells (P ≤ 0.001). In M1 macrophages, it lowered CD80 expression [geometric mean fluorescence intensity (GMFi)] by 30–40%. Although M0 macrophages showed a significant increase in CD200R (P ≤ 0.001), M2 macrophages showed no change. Supernatants from UV-exposed keratinocytes did not affect surface markers in M0, M1 and M2 macrophages, although niacinamide treatment approximately halved CD80 expression (GMFi) in M1 macrophages exposed to these supernatants. Furthermore, niacinamide significantly decreased ROS in lipopolysaccharide (LPS)-treated M0, M1 and M2 macrophages (P ≤ 0.001) and significantly reduced caspase-1 activity in LPS + nigericin-treated M0, M1 and M2 macrophages (P ≤ 0.01).
Conclusions
Niacinamide improves macrophage viability and influences their polarization towards resolving subtype by enhancing M2 marker expression and by reducing proinflammatory M1 markers, such as CD80. Additionally, niacinamide reduces macrophage inflammatory responses by lowering ROS levels and caspase-1 activity, suggesting its potential to mitigate macrophage-driven inflammation and promote resilience to environmental stressors.