Inhibition of glycolipid biosynthesis by N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin protects against the inflammatory response in hapten-induced colitis

Int Immunopharmacol. 2004 Jul;4(7):939-51. doi: 10.1016/j.intimp.2004.04.008.

Abstract

Since glycolipid biosynthesis is potentially involved in immunological and inflammatory responses, we tested the effect of a novel inhibitor of intracellular glycolipid biosynthesis N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin (AMP-DNM) in two hapten-induced colitis models: trinitrobenzene sulphonic acid (TNBS)- and oxazolone (4-ethoxymethylene-2phenyl-2oxazoline-5-one; Oxa)-induced colitis. AMP-DNM was given either by intraperitoneal injection or orally via the diet. Mice treated with AMP-DNM had less severe colitis and a more rapid weight recovery, less edema and less wall thickness. Cellular infiltration, goblet cell loss and myeloperoxidase (MPO) activity were reduced in colons of AMP-DNM-treated animals. Intralesional IFN-gamma and IL-18 production were lower in mice of the AMP-DNM-treated groups. Furthermore, AMP-DNM treatment reduced the serum anti-TNBS and anti-Oxa antibody levels. Our findings show that the glycolipid biosynthesis inhibitor AMP-DNM has a strong anti-inflammatory and immune suppressive activity on both TNBS- and Oxa-induced colitis. The data also provide evidence that glycolipid biosynthesis is involved in the inflammatory cascade in these inflammatory bowel disease (IBD) models.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / administration & dosage
  • 1-Deoxynojirimycin / analogs & derivatives*
  • 1-Deoxynojirimycin / pharmacology*
  • Adamantane / administration & dosage
  • Adamantane / analogs & derivatives*
  • Adamantane / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antibodies / blood
  • Body Weight / drug effects
  • Colitis / chemically induced
  • Colitis / pathology
  • Colitis / prevention & control*
  • Colon / enzymology
  • Colon / pathology
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology
  • Glycolipids / biosynthesis
  • Glycolipids / metabolism*
  • Haptens / administration & dosage
  • Haptens / immunology
  • Immunoglobulin G / blood
  • Immunosuppressive Agents / pharmacology*
  • Interferon-gamma / antagonists & inhibitors
  • Interleukin-18 / antagonists & inhibitors
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxazolone / administration & dosage
  • Peroxidase / analysis
  • Peroxidase / antagonists & inhibitors
  • Trinitrobenzenesulfonic Acid / administration & dosage

Substances

  • Anti-Inflammatory Agents
  • Antibodies
  • Enzyme Inhibitors
  • Glycolipids
  • Haptens
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Interleukin-18
  • N-(5-adamantane-1-yl-methoxy-pentyl)deoxynojirimycin
  • Oxazolone
  • 1-Deoxynojirimycin
  • Interferon-gamma
  • Trinitrobenzenesulfonic Acid
  • Peroxidase
  • Adamantane