Abstract
Plants rich in luteolin have been used as Chinese traditional medicines for inflammatory diseases, hypertension, and cancer. However, little is known about the effect of luteolin on the apoptosis or autophagy of the macrophages. In this study, mouse macrophage ANA-1 cells were incubated with different concentrations of luteolin. The viability of the cells was determined by an MTT assay, apoptosis was determined by flow cytometric analysis, the level of cell autophagy was observed by confocal microscopy, and the expression levels of apoptotic or autophagic and antiapoptotic or antiautophagic proteins were detected by Western blot analysis. The results showed that luteolin decreased the viability of ANA-1 cells and induced apoptosis and autophagy. Luteolin induced apoptosis accompanied by downregulation of the expression of Bcl-2 and upregulation of the expression of caspase 3 and caspase 8. And luteolin increased FITC-LC3 punctate fluorescence accompanied by the increased expression levels of LC3-I, ATG7, and ATG12, while it suppressed the expression level of Beclin-1. Luteolin treatment resulted in obvious activation of the p38, JNK, and Akt signaling pathways, which is important in modulating apoptosis and autophagy. Thus, we concluded that luteolin induced the apoptosis and autophagy of ANA-1 cells most likely by regulating the p38, JNK, and Akt pathways, inhibiting the activity of Bcl-2 and Beclin-1 and upregulating caspase 3 and caspase 8 expression. These results provide novel insights into a therapeutic strategy to prevent and possibly treat macrophage-related diseases through luteolin-induced apoptosis and autophagy.
Highlights
Macrophages fulfill a broad range of functions in phagocytosis, microbial killing, host defense, tissue homeostasis and repair, pathology and development, and their proliferation; migration and apoptosis have been emerged as important therapeutic targets for a variety of human diseases [1, 2]
To examine the effects of luteolin on cell viability, the ANA-1 cells were exposed to different concentrations (0, 5, 10, 20, 40, 80, and 160 μM) of luteolin for 24 h or 48 h and cell viability was measured by MTT assay
80 μM luteolin reduced cell viability by 73% or more after 24 h or 48 h of treatment. These results indicate that luteolin significantly decreases the viability of ANA-1 cells, and the half maximal inhibitory concentration (IC50) was about 40 μM in the cell line
Summary
Macrophages fulfill a broad range of functions in phagocytosis, microbial killing, host defense, tissue homeostasis and repair, pathology and development, and their proliferation; migration and apoptosis have been emerged as important therapeutic targets for a variety of human diseases [1, 2]. Macrophages are critically involved in diseases that are caused by chronic inflammation (e.g., arthritis, multiple sclerosis, inflammatory bowel diseases, atherosclerosis, and cardiovascular disease) [3,4,5,6]. The apoptosis and autophagy dysfunction of the macrophage impact the development of chronic inflammation (e.g., atherosclerosis, tuberculosis, and sepsis) [7,8,9,10]. Plants rich in luteolin (3′,4′,5,7-tetrahydroxylavone), an active polyphenolic compound, have been used as Chinese traditional medicine to treat inflammatory diseases, hypertension, and cancer for a long period of time [11]. The pharmacological activities of luteolin, such as antioxidant, radical scavenging, cytoprotective, anti-inflammatory, antiallergic, and antitumor properties [12, 13], have been observed, suggesting that luteolin might possess diverse health benefits. Despite the well-documented antioxidant, anti-inflammatory, and antineoplastic potential of luteolin, little is known about the effect of luteolin on the apoptosis or autophagy of the macrophages
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