IngentaConnect Glucocorticoids and IL-10, but not 6-MP, 5-ASA or sulfasalazine b...

Authors: Oshima, T.¹; Pavlick, K.¹; Grisham, M. B.¹; Jordan, P.²; Manas, K.²; Joh, T.³; Itoh, M.³; Alexander, J. S.¹

Source: Alimentary Pharmacology & Therapeutics, Volume 15, Number 8, August 2001 , pp. 1211-1218(8)

Publisher: Blackwell Publishing

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-α 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-α (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-α on endothelial cells. Either dexamethasone or IL-10: reduced TNF-α-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.

Document Type: Research article

DOI: 10.1046/j.1365-2036.2001.01048.x

Affiliations: 1: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA 2: Department of Gastroenterology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA 3: Department of Gastroenterology, Nagoya City University Medical School, Nagoya, Japan

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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