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Glucocorticoids and IL-10, but not 6-MP, 5-ASA or sulfasalazine block endothelial expression of MAdCAM-1: implications for inflammatory bowel disease therapy.

AbstractBACKGROUND:
Enhanced MAdCAM-1 (mucosal addressin cell adhesion molecule-1) expression is associated with the aetiology of inflammatory bowel disease, but little is known about MAdCAM-1: regulation, or how inflammatory bowel disease therapies modulate MAdCAM-1.
AIM:
To examine how agents currently used to treat inflammatory bowel disease affect MAdCAM-1: induced by tnf-alpha in an in vitro model of inflammatory bowel disease.
METHODS:
Endothelial monolayers were pretreated with dexamethasone (DEX): 5-aminosalicylic acid (5-ASA), 6-mercaptopurine (6-MP), sulfasalazine or interleukin-10: (IL-10: prior to TNF-alpha (20 ng/mL), and MAdCAM-1: measured by Western blotting, RT-PCR, EMSA and lymphocyte adhesion assays.
RESULTS:
MAdCAM-1: was induced dose- and time-dependently by TNF-alpha on endothelial cells. Either dexamethasone or IL-10: reduced TNF-alpha-induced MAdCAM-1: protein, mRNA and lymphocyte adhesion. However, neither 5-ASA, sulfasalazine nor 6-MP blocked MAdCAM-1 induction.
CONCLUSIONS:
Our data indicate that dexamethasone or IL-10 can exert therapeutic activity in inflammatory bowel disease through MAdCAM-1 inhibition. 5-ASA, sulfasalazine and 6-MP, while beneficial in inflammatory bowel disease, do not directly control MAdCAM-1, and are beneficial through inhibition of other inflammatory processes.
AuthorsT Oshima, K Pavlick, M B Grisham, P Jordan, K Manas, T Joh, M Itoh, J S Alexander
JournalAlimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 15 Issue 8 Pg. 1211-8 (Aug 2001) ISSN: 0269-2813 [Print] England
PMID11472325 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cell Adhesion Molecules
  • Glucocorticoids
  • Immunoglobulins
  • Immunosuppressive Agents
  • Madcam1 protein, mouse
  • Mucoproteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Sulfasalazine
  • Mesalamine
  • Dexamethasone
  • 6-Mercaptopurine
  • Thymidine Kinase
  • thymidine kinase 1
Topics
  • 6-Mercaptopurine (pharmacology)
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
  • Cell Adhesion Molecules
  • Cells, Cultured
  • Dexamethasone (pharmacology)
  • Endothelium (drug effects)
  • Glucocorticoids (pharmacology)
  • Immunoglobulins (biosynthesis, genetics, metabolism)
  • Immunosuppressive Agents (pharmacology)
  • Inflammatory Bowel Diseases (drug therapy, etiology)
  • Interleukin-10 (pharmacology)
  • Lymphocytes (drug effects)
  • Mesalamine (pharmacology)
  • Mice
  • Mucoproteins (biosynthesis, genetics, metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfasalazine (pharmacology)
  • Thymidine Kinase (metabolism)
  • Tumor Necrosis Factor-alpha (pharmacology)

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