Using metabolic labeling techniques in human intestinal epithelial cell lines in tissue culture and in situ hybridization techniques in normal and inflamed (Crohn's) intestine, recent studies have shown that there is synthesis of acute phase proteins in enterocytes. Moreover, these studies have shown that acute phase protein biosynthesis in enterocytes is regulated by inflammatory cytokines in a manner characteristic of the physiologic acute phase response. In the course of these studies it was noticed that one inflammatory cytokine, interleukin-6 (IL-6), mediated selective down- regulation of the enterocyte-specific, differentiation-dependent integral membrane protein sucrase-isomaltase (SI) in the Caco2 intestinal epithelial cell line. In the current study we examined the effect of several other inflammatory cytokines interleukin-1 (IL-1β), tumor necrosis factor (TNFα), and interferon γ (IFNγ) on synthesis of SI in Caco2 cells, examined the possibility that inflammatory cytokines affect the synthesis of other enterocyte integral membrane proteins using lactase as a prototype, and examined the possibility that SI gene expression was down-regulated in villous enterocytes in vivo during the local inflammatory response of Crohn's disease. The results show that IL-6 and IFNγ each mediate a decrease and TNFα mediates an increase in synthesis of SI in Caco2 cells. The magnitude of down-regulation by IL-6 and IFNγ is significantly greater than the up- regulation by TNFα. IL-1β has no effect on synthesis of SI. Synthesis of lactase is not affected by any of the cytokines. There is a marked specific decrease in SI gene expression in villous enterocytes in acutely inflamed Crohn's ileum as compared to adjacent uninflamed ileum and normal ileum. Taken together, these data show that inflammatory cytokines have specific and selective effects on the expression of the brush border hydrolase SI in tissue culture and in vivo and provide evidence for a previously unrecognized mechanism for disaccharidase deficiency in intestinal inflammation.

Original languageEnglish
Pages (from-to)1237-1242
Number of pages6
JournalJournal of Biological Chemistry
Issue number2
StatePublished - Jan 12 1996


Dive into the research topics of 'Regulation of sucrase-isomaltase gene expression in human intestinal epithelial cells by inflammatory cytokines'. Together they form a unique fingerprint.

Cite this