Objective To investigate the role of lysine-specific demethylase 1 (LSD1) in the process of THP-1 monocyte-to-macrophage differentiation.Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting were performed to analyze the expression of LSD1 and interleukin-6 (IL-6) in THP-1 monocytes and THP-1-derived macrophages.Chromatin immunoprecipitation (ChIP) assay was applied to detect the occupancy of LSD1 and H3K4 methylation at IL-6 promoter during THP-1 monocyte-to-macrophage differentiation.IL-6 mRNA level and H3K4 methylation at IL-6 promoter were analyzed using qRT-PCR and ChIP assay in LSD1-knockdown THP-1 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 0,4,8,12,and 24 hours.Fluorescence activated flow cytometry was performed to reveal the percentage of macrophages differentiated from THP-1 monocytes.Results The expression of LSD1 reduced during THP-1 monocyte-to-macrophage differentiation (P<0.01).LSD1 occupancy decreased and H3K4 methylation increased at IL-6 promoter during the differentiation.With knockdown of LSD1,H3K4 methylation at IL-6 promoter was found increased after TPA treatment at different times points (all P<0.05,except 24 hours).The percentage of macrophages increased significantly in the THP-1 cells with LSD1 knockdown (P<0.05).Conclusions LSD1 is repressed during the monocyte-to-macrophage differentiation of THP-1 cells.Suppression of LSD1-mediated H3K4 demethylation may be required for THP-1 monocyte-to-macrophage differentiation. Objective To investigate the role of lysine-specific demethylase 1 (LSD1) in the process of THP-1 monocyte-to-macrophage differentiation. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting were performed to analyze the expression of LSD1 and interleukin-6 (IL-6) in THP-1 monocytes and THP-1-derived macrophages. Chromatin immunoprecipitation (ChIP) assay was applied to detect the occupancy of LSD1 and H3K4 methylation at IL-6 promoter during THP- 1 monocyte-to-macrophage differentiation. IL-6 mRNA level and H3K4 methylation at IL-6 promoter were analyzed using qRT-PCR and ChIP assay in LSD1-knockdown THP-1 cells treated with 12-O-tetradecanoylphorbol- ) for 0, 4, 8, 12, and 24 hours. Fluorescence activated flow cytometry was performed to reveal the percentage of macrophages differentiated from THP-1 monocytes. Results The expression of LSD1 reduced during THP-1 monocyte-to-macrophage differentiation P <0.01) .LSD1 occupancy decreased a nd H3K4 methylation increased at IL-6 promoter during the differentiation. Knockdown of LSD1, H3K4 methylation at IL-6 promoter was found increased after TPA treatment at different times points (all P <0.05, except 24 hours). percentage of macrophages increased significantly in THP-1 cells with LSD1 knockdown (P <0.05) .Conclusions LSD1 is repressed during the monocyte-to-macrophage differentiation of THP-1 cells. Suppression of LSD1-mediated H3K4 demethylation may be required for THP-1 monocytes -to-macrophage differentiation.