CYTOKINES MODULATE FIBROBLAST PHENOTYPE AND EPITHELIAL-STROMA INTERACTIONS IN RAT INTESTINE

Background & Aims: Homeostasis of the intestinal epithelium depends on interactions with the underlying connective tissue that may be altere d during the pathogenesis of disease. The aim of this study was to est ablish whether fibroblast phenotype can influence morphogenesis and di fferentiation of the gut epithelium. Methods: Permanently growing, non tumorigenic, homogenous fibroblast lines were established from postnat al rat intestinal mucosa. Their phenotypic characterization included t heir growth response to cytokines and expression of cytoskeletal and m embrane markers, as well as expression of basement membrane components , laminin 1 and collagen IV. Their influence on epithelial growth, fun ctional polarization, and morphogenesis was analyzed using coculture a nd tissue grafting of the fibroblast lines with fetal gut endoderm. Re sults: Two intestinal fibroblast lines are described, one that support s normal intestinal morphogenesis and differentiation, and one that in duces growth of fetal epithelial cells. Among the phenotypic differenc es between the two lines, the former differentiates into myofibroblast s in response to transforming growth factor beta 1 and, in basal condi tions, expresses twice as much laminin than the latter. The growth of the two lines is also affected differentially by transforming growth f actor beta 1 and interleukin 2. Conclusions: Cytokines, which are expr essed in association with inflammation, regulate fibroblast differenti ation. Fibroblasts may modify the function and organization of the ove rlying intestinal epithelium.