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Anti-inflammatory drugs and endothelial cell adhesion molecule expression in murine vascular beds

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
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  • 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
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