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Open Access Research article

Transfection of IL-10 expression vectors into endothelial cultures attenuates α4β7-dependent lymphocyte adhesion mediated by MAdCAM-1

Makoto Sasaki1, Paul Jordan2, Jeff Houghton1, Xianmin Meng4, Makoto Itoh3, Takashi Joh3 and J Steven Alexander1*

Author Affiliations

1 Louisiana State University Health Sciences Center-Shreveport (LSUHSC-S) Molecular and Cellular Physiology, 1501 Kings Highway, Shreveport, LA, USA

2 LSUHSC-S Gastroenterology, 1501 Kings Highway, Shreveport, LA, USA

3 Nagoya City University Graduate School of Medical Sciences Department of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi Mizuho-ku, Nagoya, Japan

4 Thomas Jefferson University Dermatology and Cutaneous Biol., 233 South 10th street, Suite 450, Philadelphia, PA, USA

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BMC Gastroenterology 2003, 3:3  doi:10.1186/1471-230X-3-3

Published: 20 February 2003

Abstract

Background

Enhanced expression of MAdCAM-1 (mucosal addressin cell adhesion molecule-1) is associated with the onset and progression of inflammatory bowel disease. The clinical significance of elevated MAdCAM-1 expression is supported by studies showing that immunoneutralization of MAdCAM-1, or its ligands reduce inflammation and mucosal damage in models of colitis. Interleukin-10 (IL-10) is an endogenous anti-inflammatory and immunomodulatory cytokine that has been shown to prevent inflammation and injury in several animal studies, however clinical IL-10 treatment remains insufficient because of difficulties in the route of IL-10 administration and its biological half-life. Here, we examined the ability of introducing an IL-10 expression vector into endothelial cultures to reduce responses to a proinflammatory cytokine, TNF-α

Methods

A human IL-10 expression vector was transfected into high endothelial venular ('HEV') cells (SVEC4-10); we then examined TNF-α induced lymphocyte adhesion to lymphatic endothelial cells and TNF-α induced expression of MAdCAM-1 and compared these responses to control monolayers.

Results

Transfection of the IL-10 vector into endothelial cultures significantly reduced TNF-α induced, MAdCAM-1 dependent lymphocyte adhesion (compared to non-transfected cells). IL-10 transfected endothelial cells expressed less than half (46 ± 6.6%) of the MAdCAM-1 induced by TNF-α (set as 100%) in non-transfected (control) cells.

Conclusion

Our results suggest that gene therapy of the gut microvasculature with IL-10 vectors may be useful in the clinical treatment of IBD.

Keywords:
IL-10; transfection; lymphocyte; MAdCAM-1