Glucosamine inhibits LPS-induced COX-2 and iNOS expression in mouse macrophage cells (RAW 264.7) by inhibition of p38-MAP kinase and transcription factor NF-kappaB

Mol Nutr Food Res. 2007 May;51(5):587-93. doi: 10.1002/mnfr.200600226.

Abstract

Glucosamine supplements are very promising nonsteroidal anti-inflammatory agents widely used for the treatment of arthritis in animals and humans. In this study, we have proposed the molecular mechanism underlying the anti-inflammatory properties of glucosamine hydrochloride (GLN) using mouse macrophage cell line (RAW 264.7). Treatment with GLN inhibited LPS-stimulated nitric oxide (NO) production. Western blotting and RT-PCR analysis showed that GLN treatment decreased LPS-induced inducible nitric-oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and mRNA expression in RAW 264.7 cells, respectively. To further elucidate the mechanism of inhibitory effect of GLN, we studied the LPS-induced phosphorylation of mitogen-activated protein kinases (pp44/42 and pp38). Our results clearly indicated that GLN treatment resulted in a reduction of pp38, whereas activation of p44/42 was not affected. In addition, LPS-induced activation of nuclear factor-kappaB (NF-kappaB) DNA binding suggests an inhibitory effect of GLN. These results indicate that GLN suppresses the LPS-induced production of NO, expression of iNOS and COX-2 by inhibiting NF-kappaB activation and phosphorylation of p38 MAP kinase.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Cell Line
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Gene Expression / drug effects
  • Glucosamine / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Macrophages / enzymology
  • Mice
  • NF-kappa B / antagonists & inhibitors*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / genetics
  • Phosphorylation / drug effects
  • RNA, Messenger / analysis
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • p38 Mitogen-Activated Protein Kinases
  • Glucosamine