Inhibition of glycolipid biosynthesis by N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin protects against the inflammatory response in hapten-induced colitis.
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.
Shen
Chong
C
Laboratory of Experimental Immunology, Catholic University of Leuven, Campus Gasthuisberg (O&N), Herestraat 49, B-3000 Leuven, Belgium.
Bullens
Dominique
D
Kasran
Ahmad
A
Maerten
Philippe
P
Boon
Louis
L
Aerts
Johannes M F G
JM
Van Assche
Gert
G
Geboes
Karel
K
Rutgeerts
Paul
P
Ceuppens
Jan L
JL
D017485:1-Deoxynojirimycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000906:Antibodies / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006017:Glycolipids / Q000096:biosynthesis / Q000378:metabolism*; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D020382:Interleukin-18 / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010081:Oxazolone / Q000008:administration & dosage; D009195:Peroxidase / Q000032:analysis / Q000037:antagonists & inhibitors; D014302:Trinitrobenzenesulfonic Acid / Q000008:administration & dosage
D000893:Anti-Inflammatory Agents; D000906:Antibodies; D004791:Enzyme Inhibitors; D006017:Glycolipids; D006241:Haptens; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D020382:Interleukin-18; C496281:N-(5-adamantane-1-yl-methoxy-pentyl)deoxynojirimycin; D010081:Oxazolone; D017485:1-Deoxynojirimycin; D007371:Interferon-gamma; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D000218:Adamantane