INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN (IGFBP)-4 EXPRESSION IN HT-29 CELLS IS DEPENDENT ON THE CARBOHYDRATE AVAILABLE IN CULTURE MEDIUM:

45 HT-29 cells are a heterogenous, pluripotent human colonic carcinoma cell line. These cells differentiate into enterocyte-like cells when grown in a glucose-free, galactose-containing (galactose) medium, whereas in glucose-containing medium they act like undifferentiated crypt cells. Thus HT-29 cells have been utilized as a model of enterocyte differentiation. Intestinal cell proliferation is stimulated by the insulin-like growth factors (IGFs), which are modulated by IGFBPs. The HT-29 cells produce IGF-II and three isoforms of IGFBP-4 and also have a biologically active interleukin (IL)-2 receptor, IL-2 being one of the proinflammatory cytokines. In other tissue types, interleukin exposure has resulted in increased IGFBP expression. This study was to examine whether interleukin treatment of enterocytes would increase their IGFBP production. The HT-29 cells were plated equally in 12-well plates and half were transitioned to galactose media. At confluence the HT-29 cells were rinsed and then incubated with medium containing either glucose or galactose plus recombinant IL-2 at physiologic doses of 0.5-1.0 ng/ml for 48h. Cell numbers and total protein production were equal. HT-29 cells grown in glucose demonstrated a 38% decrease in IGFBP-4 present on ligand blotting. In contrast, the HT-29 cells grown in galactose demonstrated a 29% increase in IGFBP-4 production. Therefore, the HT-29 cellular IGFBP-4 response to a proinflammatory cytokine differs depending on if the growth conditions favor an undifferentiated or a differentiated status. These findings indicate that the IGF-IGFBP axis in enterocytes can be altered in response to interleukins and therefore this axis could be changed in inflammatory conditions of the bowel such as the inflammatory bowel diseases.