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

Abstract

Edited by Dennis R. VoelkerWe 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-␣ mRNAs under 25 mM glucose conditions yet did not inhibit upregulation under 5 mM glucose conditions. Glucose itself dose dependently increased LPS-induced iNOS expression. LPS-induced MAPK and IB-␣ phosphorylation did not significantly differ at normal and high glucose conditions. The activity of LPS-induced nuclear factor-B (NF-B) 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-B 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-B 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.

Glucosamine has an antiallergic effect in mice with allergic asthma and rhinitis

“…Glucosamine (2‐amino‐2‐deoxy‐ d ‐glucose; GlcN) is a sugar synthesized from glucose by the hexosamine biosynthetic pathway in nearly all types of cells in the body . Exogenous GlcN can enter the cell by passing through glucose transporters (GLUT‐1, GLUT‐2, and GLUT‐4) and induce an increase in UDP‐ N ‐acetyl‐GlcN (UDP‐GlcNAc).…”

Beneficial Effects of Some Nutraceuticals Containing Glucosamine and Antioxidant against CCL4 Induced Brain Injury in Rats

“…and D2 have anti-inflammatory effect beside their antioxidant one. In the same manner, Hwang et al [9] reported that GlcN or its derivatives may serve as novel neuroprotective or anti-inflammatory agents. Also, the GSH contents in the groups co-administered AM, D1, and D2 with CCl 4 were significantly increased compared with CCl 4 group (D1 > D2 > AM).…”

“…Other pharmacological properties of GlcN including protective effects against multiple sclerosis and encephalomyelitis (Zhang et al [5]), learning and memory impairment (Jamialahmadi et al [6]), colitis (Yomogida et al [7]), and ischemic brain injury (Hwang et al [8]) have been investigated. Recent studies further suggest that OGlcN Acylation is involved in the regulation of inflammation and exerts protective effects against inflammation-induced tissue injury, both in the brain and peripheral system (Hwang et al [9], He et al [10] and Zhang et al [11]). Hwang et al [12] showed that GlcN protects against lethal septic shock and sepsis-induced lung inflammation and injury in mouse model, and examined the potential underlying mechanism.…”

LPS induces GFAT2 expression to promote O-GlcNAcylation and attenuate inflammation in macrophages

“…However, contradictory results have been obtained concerning the effect of TLR4 activation on protein O-GLNAcylation. Indeed, depending on the experimental setting, both increases [22,23] and decreases [24,25] in the general O-GlcNAcylation profile were observed upon LPS stimulation.…”