209 - Luteolin Exerts Anti-Inflammatory Effects through Regulating Functional Diversity of Macrophage Phenotypes

Abstract

Objectives Macrophages (Mφ) play major roles in innate immunity for host defense against infection with bacteria. Activated Mφ are classified into M1 and M2 phenotypes. Pro-inflammatory M1-Mφ have the function of phagocytosis and bactericidal activity. In contrast, M2-Mφ play an anti-inflammatory role and can decrease M1-derived immune reaction. However, an excessive or prolonged M1 polarization leads to tissue injury and chronic inflammation. Thus, it is an important to regulate M1/M2 balance. In this study, we investigated whether luteolin, including in many vegetables and fruit, affects M1 or M2 polarization, and this functional diversity. Materials & Methods Polarization of mice bone marrow-derived Mφ (BMDMs) was induced by lipopolysaccharide (LPS) and interferon (IFN)-γ to M1-Mφ) or by interleukin (IL) -4 and IL-13 to M2-Mφ. Additionally, BMDMs were cultured with luteolin during activation to M1 or M2 phenotype. The expressions of hypoxia inducible factor-1α (HIF-1α), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF-α) for M1-marker, and mannose receptor (MR), arginase-1 and Ym-1 for M2-marker were determined by Western blot or quantitative real-time PCR. Nitrogen oxides (NOx) and phorbol 12-myristate 13-acetate-induced reactive oxygen species (ROS) production were measured by Griess reaction and chemiluminescence assay, respectively. Results Mφ activated by LPS and IFN-γ increased the protein and mRNA levels for M1-marker and the productions of NOx and ROS. Mφ activated by IL-4 and IL-13 were up-regulated the expressions for M2-marker. Luteolin inhibited the increased in the expressions of each of marker. Both NOx and ROS production were suppressed by luteolin. Conclusion These results suggested that luteolin may modulate activation to M1/M2-Mφ from naive Mφ. It will be also discussed the effect of luteolin on microbicidal function in each polarization.