Transfection of IL-10 expression vectors into endothelial cultures attenuates alpha4beta7-dependent lymphocyte adhesion mediated by MAdCAM-1.

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-alpha

METHODS:

A human IL-10 expression vector was transfected into high endothelial venular ('HEV') cells (SVEC4-10); we then examined TNF-alpha induced lymphocyte adhesion to lymphatic endothelial cells and TNF-alpha 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-alpha 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-alpha (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.

• Authors: Makoto Sasaki, Paul Jordan, Jeff Houghton, Xianmin Meng, Makoto Itoh, Takashi Joh, J Steven Alexander
• Journal: BMC gastroenterology (BMC Gastroenterol) Vol. 3 Pg. 3 (Feb 20 2003) ISSN: 1471-230X [Electronic] England
• PMID: 12625840 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cell Adhesion Molecules
• Immunoglobulins
• Integrin alpha Chains
• MADCAM1 protein, human
• Mucoproteins
• Receptors, Lymphocyte Homing
• Tumor Necrosis Factor-alpha
• Interleukin-10

Topics

• Adhesiveness
• Cell Adhesion Molecules
• Cells, Cultured
• Endothelium (cytology, metabolism)
• Genetic Therapy (methods)
• Genetic Vectors
• Humans
• Immunoglobulins (metabolism)
• Inflammatory Bowel Diseases (therapy)
• Integrin alpha Chains (metabolism)
• Interleukin-10 (metabolism)
• Mucoproteins (metabolism)
• Receptors, Lymphocyte Homing (metabolism)
• Transfection
• Tumor Necrosis Factor-alpha (physiology)