EVIDENCE FOR AN ACUTE-PHASE RESPONSE IN HUMAN INTESTINAL EPITHELIAL-CELLS

During the host response to inflammation/tissue in jury there are many changes in intermediary metabolism including a dramatic change in the concentration of many 'acute phase'' plasma proteins. Although many o f these acute phase proteins are predominantly derived from the liver and the response can be elicited from liver cells incubated in tissue culture with cytokines such as interleukin-6 (IL-6), interleukin-I (IL -1), tumor necrosis factor-alpha, interferon-gamma, leukemia inhibitor y factor, interleukin-11 (IL-11), and oncostatin M, there is now evide nce that the response can also be elicited in extrahepatic tissues and cell types. In this study, we show that many of the acute phase plasm a proteins are expressed in human intestinal epithelial cell lines Cac o2 and T84 and that their expression is induced or regulated by cytoki nes IL-6, IL-1, interferon, and tumor necrosis factor in a manner char acteristic of the acute phase response. In fact, effects of IL-1 and I L-6 which are additive, synergistic, and antagonistic in liver cell li nes are also observed in these intestinal epithelial cell lines. Respo nses to IL-6 and IL-1 are seen at all stages of differentiation of Cac o2 cells from crypt-like enterocytes to villus-like enterocytes. Caco2 cells express binding sites for IL-6 at both poles, for IL-I at the b asolateral pole and, to a lesser extent, at the apical pole. T84 cells have IL-1 and IL-6 receptor binding sites only at the basolateral pol e. IL-6 and IL-1 also regulate the expression of enterocyte-specific i ntegral membrane proteins as exemplified by down-regulation of sucrase -isomaltase gene expression in response to IL-6. These data raise the possibility that enterocytes are involved in a local response to injur y/inflammation at the epithelial surface and establish a model system for examining coordination of the acute phase response in a bipolar ce ll.