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

Abstract

BACKGROUND:

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.

• Authors: T Oshima, K Pavlick, M B Grisham, P Jordan, K Manas, T Joh, M Itoh, J S Alexander
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 15 Issue 8 Pg. 1211-8 (Aug 2001) ISSN: 0269-2813 [Print] England
• PMID: 11472325 (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
• Mercaptopurine
• Thymidine Kinase
• thymidine kinase 1

Topics

• 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)
• Mercaptopurine (pharmacology)
• Mesalamine (pharmacology)
• Mice
• Mucoproteins (biosynthesis, genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sulfasalazine (pharmacology)
• Thymidine Kinase (metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)