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[Inhibition of Demethylation of Protein Phosphatase 2A Catalytic Subunit (PP2Ac) Promotes M1 Polarization of Macrophages]

[Inhibition of Demethylation of Protein Phosphatase 2A Catalytic Subunit (PP2Ac) Promotes M1 Polarization of Macrophages]

Laiming Mo, Ling Meng, Li Lan, Shengboxiaoji Chang, Cailing Lu, Xiyi Li, Shen Tang

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2018 Jul;34(7):595-599.

PMID: 30381122

Abstract:

Objective To investigate the role of demethylation of protein phosphatase 2A catalytic subunit (PP2Ac) on M1 macrophage polarization. Methods THP-1 cells were induced to differentiate into M0 macrophages with phorbol ester (PMA) for 24 hours, and then stimulated to differentiate into M1 macrophages induced by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) for 48 hours. The administration group and the solvent control group were respectively cultured with 0.5 μmol/L ABL127 and the same volume of DMSO for 48 hours on M1 macrophage polarization models. Inverted microscope was used to observe the morphological changes of macrophages. The mRNA expression levels of cyclooxygenase 2 (COX-2), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and C-X-C motif chemokine ligand 10 (CXCL10) in M1 macrophages were detected by quantitative real-time PCR. M1 macrophage phagocytosis was determined by neutral red uptake assay. Western blot analysis was applied to test the level of PP2Ac demethylation. Results In the differentiation of M0 into M1 macrophages, the cells were elongated and became spindle-shaped. Furthermore, the expression of M1 macrophage markers including COX-2, TNF-α, IL-6 and CXCL10 significantly increased and phagocytosis was enhanced, but PP2Ac demethylation was decreased. Compared with the DMSO group, PP2Ac demethylation decreased while spindle cells, phagocytosis, and the mRNA levels of COX-2, TNF-α, IL-6 and CXCL10 significantly increased in the administration group with 0.5 μmol/L ABL127. Conclusion The inhibition of PP2Ac demethylation promotes the differentiation of M1 macrophages, and increases the expression of pro-inflammatory cytokines and the phagocytosis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1073529415	ABL127		1073529-41-5	Price

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