Article Text
Abstract
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.
Aims 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 α 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.
- P-selectin
- E-selectin
- intercellular adhesion molecule 1
- vascular cell adhesion molecule 1
- dexamethasone
- 5-aminosalicylic acid
Abbreviations
- 5-ASA
- 5-aminosalicylic acid
- 6-MP
- 6-mercaptopurine
- CAM
- cell adhesion molecule
- DEX
- dexamethasone
- IBD
- inflammatory bowel disease
- ICAM
- intercellular adhesion molecule
- LPS
- lipopolysaccharide
- MTX
- methotrexate
- TNF
- tumour necrosis factor
- VCAM
- vascular cell adhesion molecule
- ECAM
- endothelial cell adhesion molecule
- PBS
- phosphate buffered saline
- BSA
- bovine serum albumin
- HUVEC
- human umbilical vein endothelial cells
- IL
- interleukin
- NF-κΒ
- nuclear factor κΒ
Statistics from Altmetric.com
- P-selectin
- E-selectin
- intercellular adhesion molecule 1
- vascular cell adhesion molecule 1
- dexamethasone
- 5-aminosalicylic acid
Abbreviations
- 5-ASA
- 5-aminosalicylic acid
- 6-MP
- 6-mercaptopurine
- CAM
- cell adhesion molecule
- DEX
- dexamethasone
- IBD
- inflammatory bowel disease
- ICAM
- intercellular adhesion molecule
- LPS
- lipopolysaccharide
- MTX
- methotrexate
- TNF
- tumour necrosis factor
- VCAM
- vascular cell adhesion molecule
- ECAM
- endothelial cell adhesion molecule
- PBS
- phosphate buffered saline
- BSA
- bovine serum albumin
- HUVEC
- human umbilical vein endothelial cells
- IL
- interleukin
- NF-κΒ
- nuclear factor κΒ