Cytokines regulate apolipoprotein B secretion by Caco-2 cells: differential effects of IL-6 and TGF-beta 1

A variety of cytokines are found in the intestinal mucosa of individuals with inflammatory diseases. The potential role of cytokines in mediating lipoprotein assembly and secretion in the human intestinal cell line, Caco-2, was investigated. Interleukin-1 beta, interleukin-6 (IL-6), and tumor necrosis factor-alpha all decreased the basolateral secretion of apolipoprotein B (apo B), with IL-6 being the most potent. IL-6 was also found to inhibit triacylglycerol secretion. In contrast, transforming growth factor-beta 1 (TGF-beta 1) increased the secretion of apo B and triacylglycerol. In pulse-chase experiments, IL-6 decreased the rate of synthesis and secretion of apo B-100 and apo B-48 without altering the rate of apo B degradation, whereas TGF-beta 1 increased the rate of synthesis and secretion of apo B-100 and apo B-48. Degradation of apo B was also not affected by TGF-beta 1. The abundance of apo B mRNA in cells incubated with IL-6 was decreased, whereas cells incubated with TGF-beta 1 had higher levels of apo B mRNA. In conditions of small intestinal inflammation, cytokines could contribute to the observed malabsorption of fat and other nutrients by the small intestine.