Abstract
During the host response to inflammation/tissue injury there are many changes in intermediary metabolism including a dramatic change in the concentrations of many "acute phase" plasma proteins. Although many of 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-1 (IL-1), tumor necrosis factor-alpha, interferon-gamma, leukemia inhibitory factor, interleukin-11 (IL-11), and oncostatin M, there is now evidence that the response can also be elicited in extrahepatic tissues and cell types. In this study, we show that many of the acute phase plasma proteins are expressed in human intestinal epithelial cell lines Caco2 and T84 and that their expression is induced or regulated by cytokines IL-6, IL-1, interferon, and tumor necrosis factor in a manner characteristic of the acute phase response. In fact, effects of IL-1 and IL-6 which are additive, synergistic, and antagonistic in liver cell lines are also observed in these intestinal epithelial cell lines. Responses to IL-6 and IL-1 are seen at all stages of differentiation of Caco2 cells from crypt-like enterocytes to villus-like enterocytes. Caco2 cells express binding sites for IL-6 at both poles, for IL-1 at the basolateral 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 pole. IL-6 and IL-1 also regulate the expression of enterocyte-specific integral 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 injury/inflammation at the epithelial surface and establish a model system for examining coordination of the acute phase response in a bipolar cell.
Highlights
IL-1 areseen at all stages of differentiation of Caco2 characterized of these cytokines include IL-6,’ IL-1, TNF, cells from crypt-like enterocytes to villus-like entero- IFN, LIF, IL-11, and oncostatin M
We demonstrated that two acute phase plasma proteins, at-antitrypsin and transferrwine,re expressed in the human intestinal epithelial cell line Caco2
The results show that al-AT is synthesized in control cells and that its synthesis is increasinedthe presence of IL-1 and IL-6
Summary
Cells is regulated by IL-6 in a manner characteristic of the acute phase response, 2) other acute phase plasma proteins Cytokines Modulate Synthesis of Acute Phase Proteins in are expressed in this enterocyticell line, and 3) the cell line Differentiated CacoP Cells-Our previous studies had shown possesses the machinery for accurately transducing the sigtnhaalst Caco cells synthesize al-AT and transferrin and that of the acute phaseresponse. APcuhtaese ResponsHe uinman IntestEinpaitlhelial Cells creased by TNF and IFN, but not affected by EGF These results indicate that Caco cells synthesize factor B and can be induced to synthesize al-ACT, that Caco2cells can respond with specific and selective changes in gene expression to IL1, IL-6, TNF, andIFNand thatthe responses to these cytokines are similar, if not identical, to responses in cultured liver cells and cell lines and tochanges in plasma concentrations during the acute phase response in humans [1,2,3,4,5,6,7,8,9,10,11,12,13]. LPS had no effect on synthesis of factor B, al-ACT, or transferrin even at relatively high concentrations (100ng/ ml).
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