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

BMC Gastroenterology

J Steven Alexander³  Takashi Joh⁴  Makoto Itoh⁴  Xianmin Meng¹  Jeff Houghton³  Paul Jordan²  Makoto Sasaki³ 

[1] Thomas Jefferson University Dermatology and Cutaneous Biol., 233 South 10th street, Suite 450, Philadelphia, PA, USA;LSUHSC-S Gastroenterology, 1501 Kings Highway, Shreveport, LA, USA;Louisiana State University Health Sciences Center-Shreveport (LSUHSC-S) Molecular and Cellular Physiology, 1501 Kings Highway, Shreveport, LA, USA;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

关键词: MAdCAM-1;    lymphocyte;    transfection;    IL-10;   

Others  :  1215899
DOI  :  10.1186/1471-230X-3-3

 received in 2002-12-12, accepted in 2003-02-20,  发布年份 2003

【 摘 要 】

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.

【 授权许可】

   
2003 Sasaki et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 图 表 】

Figure 1.

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