Regulation of ICAM-1-mediated fibroblast-T cell reciprocal interaction: implications for modulation of gut inflammation.
Gastroenterology
; 117(3): 546-56, 1999 Sep.
Article
en En
| MEDLINE
| ID: mdl-10464130
ABSTRACT
BACKGROUND & AIMS:
Immune-nonimmune cell interactions modulate mucosal immunity. We investigated the expression of adhesion molecules by intestinal fibroblasts, the effect of immune cell-derived factor on fibroblast binding of T cells, and the consequences of interfering with adhesion molecule expression on fibroblast-T cell interaction.METHODS:
Expression of fibroblast intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 surface and messenger RNA (mRNA) was measured before and after exposure to immune cell-derived supernatants. Fibroblasts were treated with antibodies to ICAM-1 or VCAM-1, or ICAM-1 antisense oligonucleotide Isis 2302, before a T-cell adhesion assay.RESULTS:
Fibroblast activation by immune cell-derived cytokines enhanced ICAM-1 and VCAM-1 surface expression and mRNA as well as adhesiveness for T cells. Blockade with neutralizing antibodies showed that binding was almost exclusively dependent on ICAM-1. Isis 2302 specifically reduced fibroblast ICAM-1 mRNA and dose-dependently inhibited ICAM-1 surface expression and T-cell binding.CONCLUSIONS:
ICAM-1 is essential for intestinal fibroblast binding of T cells, a phenomenon that is efficiently and specifically disrupted by ICAM-1 antisense oligonucleotides. These observations emphasize the crucial regulatory role of fibroblasts in mucosal immunity and their potential as targets for therapeutic intervention in intestinal inflammation.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T
/
Molécula 1 de Adhesión Intercelular
/
Fibroblastos
/
Mucosa Intestinal
Límite:
Humans
Idioma:
En
Revista:
Gastroenterology
Año:
1999
Tipo del documento:
Article
País de afiliación:
Estados Unidos