Cytokines modulate fibroblast phenotype and epithelial-stroma interactions in rat intestine.
OBJECTIVE
Homeostasis of the intestinal epithelium depends on interactions with the underlying connective tissue that may be altered during the pathogenesis of disease. The aim of this study was to establish whether fibroblast phenotype can influence morphogenesis and differentiation of the gut epithelium.


METHODS
Permanently growing, nontumorigenic, homogenous fibroblast lines were established from postnatal rat intestinal mucosa. Their phenotypic characterization included their growth response to cytokines and expression of cytoskeletal and membrane markers, as well as expression of basement membrane components, laminin 1 and collagen IV. Their influence on epithelial growth, functional polarization, and morphogenesis was analyzed using coculture and tissue grafting of the fibroblast lines with fetal gut endoderm.


RESULTS
Two intestinal fibroblast lines are described, one that supports normal intestinal morphogenesis and differentiation, and one that induces growth of fetal epithelial cells. Among the phenotypic differences between the two lines, the former differentiates into myofibroblasts in response to transforming growth factor beta1 and, in basal conditions, expresses twice as much laminin than the latter. The growth of the two lines is also affected differentially by transforming growth factor beta1 and interleukin 2.


CONCLUSIONS
Cytokines, which are expressed in association with inflammation, regulate fibroblast differentiation. Fibroblasts may modify the function and organization of the overlying intestinal epithelium.
Fritsch
C
C
INSERM Unite 381, Ontogenese et Pathologie du Systeme Digestif, Strasbourg, France.
Simon-Assmann
P
P
Kedinger
M
M
Evans
G S
GS
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002642:Chick Embryo; D002999:Clone Cells; D003094:Collagen / Q000096:biosynthesis; D004847:Epithelial Cells; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007422:Intestines / Q000166:cytology* / Q000187:drug effects; D007797:Laminin / Q000096:biosynthesis; D051379:Mice; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007376:Interleukin-2; D007797:Laminin; D016212:Transforming Growth Factor beta; D003094:Collagen