Presentationsbeen proposed for this: induction of IL-13Ra2 expression on the surface membrane by signalling of IL-13 through the IL-13Ra1 receptor in the presence of TNF-a, followed by IL-13 signalling through IL-13Ra2.Signalling via this route in macrophages induced production of TGF-b, potentially leading to collagen synthesis and fibrosis.Therefore, the aim of this study is to determine whether this two-step process occurs in human intestine and particularly if it occurs in collagen-producing intestinal fibroblasts.Using intestinal tissue taken from patients with CD, ulcerative colitis (UC) or cancer, the preliminary immunohistology data suggests that both IL-13 receptors are expressed in the intestinal muscle and mucosa of all patients, and appear to be co-expressed on the same cells which, phenotypically, are stromal or epithelial cells.There seems to be little difference in either the number of IL-13R + cells present, or the appearance of the cells, between cancer and UC tissue.However, in the muscle layer of fibrotic areas of CD tissue, IL-13Ra1/Ra2 double positive cells appear to be enlarged.Fibroblast lines generated from all tissue samples retain the expression of IL-13Ra1 but Ra2 expression was variable, as determined by immunofluorescence.These receptors are able to signal since induction of phosphorylated stat 6 was detected by Western blotting in cell lysates generated from cell lines treated with IL-13, with maximum stimulation at 60 minutes, while there was no change in the level of total stat 6 over the same period.Initial studies in cell lines treated with IL-13 indicate increased collagen synthesis and decreased TIMP-1 and TIMP-2, as detected by ELISA on cell culture supernatants.Upregulation of IL-13Ra2 was observed in cell lines treated with IL-13 and TNF-a, in comparison with untreated cells, quantified by Western blotting.In summary, our data are consistent with the hypothesis that signalling through IL-13 receptors in mesenchymal cells contributes to the fibrotic process in CD.We propose, therefore, that IL-13 and its receptors may be considered as targets for future therapy.