Expression of functional ICAM-1 and VCAM-1 adhesion molecules by an immortalized epithelial cell clone derived from the small intestine

Xian Chang Li, Anthony M. Jevnikar, David R. Grant

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The role of small bowel-derived epithelial cells in regulating the accumulation of inflammatory cells within the inflamed gut epithelium is poorly understood because of the difficulties in culturing the epithelial cells in vitro. We have recently developed a cloned epithelial cell line (IEC-4.1) derived from the small intestine of BALB/c mice. In the present study, we examined whether IEC-4.1 cells could express adhesion molecules ICAM-1 and VCAM-1 and the molecular basis of macrophage adhesion to the epithelial cells. Northern blot analysis demonstrated that IEC-4.1 cells constitutively expressed ICAM-1 and VCAM-1 mRNA at low levels. Stimulation with LPS (12 μg/ml) or TNF-α (2.5 ng/ml) markedly upregulated ICAM-1 and VCAM-1 gene expression in IEC-4.1 cells. ICAM-1 mRNA started to increase 2 hr after LPS stimulation, peaked at 4 hr, and then decreased rapidly to the basal level at 8 hr. VCAM-1 mRNA had the similar pattern of upregulation but the increased VCAM-1 mRNA sustained over a longer period of time and did not return to the basal level until 24 hr after the stimulation. IEC-4.1 cells expressed very low basal levels of ICAM-1 and VCAM-1 on the cell surface as demonstrated by immunofluorescence staining and FACS analysis. Stimulation of IEC-4.1 cells with LPS or TNF-α markedly increased the surface expression of both ICAM-1 and VCAM-1, which correlated with the increased binding of macrophages to the stimulated IEC-4.1 cells. Adherence of macrophages to the IEC-4.1 cells was mediated by both LFA-1/ICAM-1 and VLA-4/VCAM-1 since blocking both adhesion pathways inhibited macrophage adhesion by about 90%. These findings suggest that small bowel-derived epithelial cells may be capable of expressing a defined set of functional adhesion molecules during mucosal inflammation.

Original languageEnglish (US)
Pages (from-to)58-66
Number of pages9
JournalCellular Immunology
Volume175
Issue number1
DOIs
StatePublished - Jan 10 1997

ASJC Scopus subject areas

  • Immunology

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