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- W855692844 abstract "Macrophages (MØs) are classified as classically-(M1) or alternatively-(M2) activated, based on their exposure to different fate-determining mediators. The post-translational modification of proteins by O-GlcNAcylation (O-GlcNAc) is highly dynamic and modulates cell-signaling processes. Acute increases in O-GlcNAc levels reduce the release of pro-inflammatory mediators and regulate inflammatory processes by decreasing e.g. NF-kB activation. This study tested the hypothesis that increased O-GlcNAc levels favor polarization of MØs to the anti-inflammatory/M2 phenotype. Macrophages obtained from bone marrow of male BALB/c mice were incubated with vehicle, glucosamine, the O-GlcNAcase inhibitors PugNAc (100 µM) and Thiamet-G (TMG, 1µM), LPS + IFN-g (1mg/ml + 200ng/ml) for M1 or interleukin-4 (IL-4, 50ng/ml) for M2 polarization. Expression of polarization markers (F4/80 and CD206) was assessed by flow cytometry. Cellular viability was not affected by these compounds, as measured by MTT reduction assay. Incubation of MØs with TMG, glucosamine and PugNAc produced a time-dependent increase in O-GlcNAc levels, determined by western blot. Incubation of undifferentiated MØs with TMG, as well as with LPS (1mg/ml), for 24h significantly increased IL-1b release. In M1-differentiated MØs, stimulation for 24h with TMG further increased IL-1b and IL-6 mRNA expression. In M2-differentiated MØs, TMG did not change arginase I expression. These preliminary results suggest that increases in O-GlcNAcylation in 24h contribute to a pro-inflammatory phenotype in macrophages. Our studies suggest that the O-GlcNAc pathway as a potential therapeutic target in diseases associated inflammatory responses." @default.
- W855692844 created "2016-06-24" @default.
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- W855692844 date "2015-04-01" @default.
- W855692844 modified "2023-09-27" @default.
- W855692844 title "Effects of augmented O ‐GlcNAcylation on activation and differentiation of macrophages" @default.
- W855692844 doi "https://doi.org/10.1096/fasebj.29.1_supplement.621.15" @default.
- W855692844 hasPublicationYear "2015" @default.
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