Potent Suppressive Effect of Resveratrol and Apigenin on Pro‐Inflammatory Responses in Lipopolysaccharide and IFN‐γ‐activated Microglia and Macrophages: Implications for Alzheimer's disease therapies

Abstract

PurposeActivation of microglia and macrophages contribute to neuroinflammation and neurotoxicity in Alzheimer's disease. However, microglia and macrophages differ in their ability to induce immune responses. Understanding the differences in the release of pro‐inflammatory factors by microglia and macrophage cells is important for identifying potential drugs to treat disease.MethodsRAW macrophages, C8B4 microglia and primary murine microglia cells were activated with lipopolysaccharide (LPS) with interferon‐γ (IFN‐γ) and levels of 23 cytokines were measured using a cytokine array. Further to this, the cells were treated with resveratrol and apigenin, anti‐inflammatories suggested as potential anti‐neurodegenerative drugs, and nitrite levels measured as a marker of oxidative stress.ResultsLPS and IFN‐γ increased nitrite levels 13 fold in RAW and 3 fold in microglia. RAW activation resulted in greater release of cytokines, such as IL‐10, whereas microglia showed greater release of chemokines, such as eotaxin. Furthermore treatment with 25 μg/ml resveratrol or 35 μg/ml apigenin lead to a 50% decrease in nitrite levels.ConclusionMicroglia and macrophages respond to activation by releasing distinct cytokine profiles. A potent suppressive effect of resveratrol and apigenin on pro‐inflammatory responses suggests a therapeutic potential for these compounds in neurodegenerative diseases.Grant Funding Source : University of Western Sydney