CYTOKINE EFFECTS IN A HUMAN COLONIC GOBLET CELL-LINE - CELLULAR-DAMAGE AND ITS PARTIAL PREVENTION BY 5-AMINOSALICYCLIC ACID

The aim of the present study was to investigate the effects of cytokines on intestinal goblet cells in vitro. For this purpose, we examined the effects of recombinant interferon gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) on the human colonic goblet cel line Cl.16E by morphological and kinetic studies, and by the assessment of mucus production during IFN-gamma/TNF-alpha treatment. Control cultures of Cl.16E cells grown on nitrocellulose filters formed monolayers of polarized goblet cells, which had kinetic characteristics similar to those of a differentiated epithelium in steady state. The combined action of IFN-gamma and TNF-alpha caused a dose-related cellular exfoliation, leading to the formation of a mucoid cap made of mucus and cellular debris. The remaining viable cells underlying the mucoid cap were cuboidal and devoid of mucus granules. A dose-related increase in cellular incorporation of [H-3]thymidine was reactive to the cytokine-induced cell loss. The synergistic effects of IFN-gamma and TNF-alpha were found to be reversible when the cells were reincubated in a culture medium without cytokines. Furthermore, 5-aminosalicylic acid partially protected Cl.16E cells against cellular injury caused by IFN-gamma and TNF-alpha. On the whole, these morphological and kinetic findings argue that the changes induced in Cl. 16E cells by IFN-gamma and TNF-alpha closely parallel those observed during the acute phase of ulcerative colitis, and show that these cytokines can regulate intestinal mucus production by modulating cellular exfoliation, thus leading probably to a reinforced protection of the damaged mucosa.