Anti-inflammatory drugs and endothelial cell adhesion molecule expression in murine vascular beds.
BACKGROUND
Inflammatory bowel diseases (IBD) are characterised by an intense infiltration of leucocytes that is mediated by adhesion molecules expressed on the surface of activated endothelial cells.


OBJECTIVE
To determine whether drugs used in the treatment of IBD, specifically dexamethasone (DEX), 5-aminosalicylic acid (5-ASA), methotrexate (MTX), and 6-mercaptopurine (6-MP), alter the expression of endothelial cell adhesion molecules (ECAMs).


METHODS
The expression of P-selectin, E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular CAM 1 (VCAM-1) in different vascular beds of C57Bl/6J mice was measured using the dual radiolabelled monoclonal antibody technique.


RESULTS
Lipopolysaccharide (LPS) elicited a profound increase in the expression of all ECAMs in the mesentery, small intestine, caecum, and distal colon. The LPS induced increase in CAM expression was not significantly affected by prior treatment with either MTX or 6-MP. However, pretreatment with either DEX or 5-ASA significantly attenuated LPS induced increases in expression of P- and E-selectin, and VCAM-1 in the majority of tissues evaluated. DEX also blunted the LPS induced increase in ICAM-1 expression in the caecum and distal colon. DEX, but not 5-ASA, largely abolished the rise in plasma tumour necrosis factor alpha elicited by LPS.


CONCLUSIONS
These findings suggest that DEX and 5-ASA may exert their beneficial therapeutic action in IBD, at least in part, by inhibiting the expression of ECAMs which mediate leucocyte adhesion and transmigration in the microvasculature.
Mori
N
N
Department of Molecular and Cellular Physiology, LSU Medical Centre, Shreveport, Louisiana 71130-3932, USA.
Horie
Y
Y
Gerritsen
M E
ME
Anderson
D C
DC
Granger
D N
DN
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007422:Intestines / Q000098:blood supply*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000187:drug effects* / Q000378:metabolism; D019087:Selectins / Q000378:metabolism; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019087:Selectins; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1