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J Biol Chem. 2017 Feb 3;292(5):1724-1736. doi: 10.1074/jbc.M116.737940. Epub 2016 Dec 7.

Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells.

Author information

1
From the Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon 22212, Korea.
2
the Department of Brain and Cognitive Sciences, Ewha Brain Institute, College of Pharmacy, and.
3
the Department of Life Sciences, The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 03760, Korea.
4
From the Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon 22212, Korea, iohan@inha.ac.kr.

Abstract

We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. At normal glucose concentrations, GlcN dose dependently increased LPS-stimulated production of NO/iNOS. However, GlcN suppressed NO/iNOS production under high glucose culture conditions. Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs under 25 mm glucose conditions yet did not inhibit up-regulation under 5 mm glucose conditions. Glucose itself dose dependently increased LPS-induced iNOS expression. LPS-induced MAPK and IκB-α phosphorylation did not significantly differ at normal and high glucose conditions. The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. In addition, we found that the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter were further increased by GlcN under normal glucose conditions. However, both O-GlcNAcylation and DNA binding of c-Rel decreased under high glucose conditions. The NF-κB inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. In addition, pyrrolidine dithiocarbamate inhibited NF-κB DNA binding and c-Rel O-GlcNAcylation only under high glucose conditions. By blocking transcription with actinomycin D, we found that stability of LPS-induced iNOS mRNA was increased by GlcN under normal glucose conditions. These results suggest that GlcN regulates inflammation by sensing energy states of normal and fuel excess.

KEYWORDS:

NF-κB; O-GlcNAcylation; O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT); glucose; inflammation

PMID:
27927986
PMCID:
PMC5290947
DOI:
10.1074/jbc.M116.737940
[Indexed for MEDLINE]
Free PMC Article

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