Abstract

BACKGROUND AND AIMS: The effects of dextran sulphate sodium (DSS) on mouse intestinal epithelial cells and intraepithelial lymphocytes were analysed to investigate the mechanism by which DSS induces colitis and tumours in mice. Cytotoxicity of DSS towards intestinal epithelial cells and intestinal intraepithelial lymphocyte hybridomas or fresh intestinal intraepithelial lymphocytes seems to have concentration, time, and cell type dependency with increasing concentrations and time causing increased cytotoxicity. RESULTS: Integrin alpha 4 expression was marginally down regulated by 0.5% of DSS, while alpha M290 expression was up regulated. DSS inhibits the binding of 9.1 gamma delta cells to both extracellular matrix (ECM) and epithelial cells. Conversely at high concentrations it increases binding to all ECM except poly-L-lysine. Various cytokines including TGF beta, interleukin 2, and tumour necrosis factor alpha as well as prostaglandin alter the expression of the integrin alpha 4 and M290 subunits at the cell surface, and also alter the adhesion of 9.1 gamma delta cells to epithelial monolayers. The expression of a large number of cell adhesion molecules expressed on intraepithelial lymphocytes is affected by a combination of the abundant gut cytokine TGF beta and DSS, suggesting that DSS induced colitis may ultimately arise from a combination of gut cytokine and DSS. DSS also triggers intraepithelial lymphocyte aggregation on all ECM coated plate tested. CONCLUSIONS: These data suggest that the potential roles of DSS induced colitis may be: (a) direct cytotoxicity; (b) interference with the normal interaction between intestinal lymphocytes, epithelial cells, and ECMs; (c) aberrant modulation of the expression of the integrin beta 7 receptors, other cell receptors, and their functions.