[Modulation of the organization of the extracellular matrix and the production of collagen by interferon gamma in three-dimensional cultures of normal and sclerodermic fibroblasts].
Recent studies have shown inhibition of collagen synthesis by interferon gamma (IFN-gamma) in monolayer human fibroblast cultures on a plastic solid phase. However, the existence of this effect in vivo has not yet been demonstrated. Three-dimensional fibroblast cultures in collagen matrices (collagen lattices or dermal equivalents) provide a more physiological model than conventional cultures and fairly closely simulate in vivo conditions. This model was used for studying effects of IFN-gamma on normal and scleroderma fibroblasts. IFN-gamma induced a dose-dependent inhibition of fibroblast-mediated retraction of collagen lattices. IFN-gamma also inhibited total protein and collagen synthesis. Scleroderma fibroblasts were especially susceptible to the inhibitory effects of IFN-gamma. Since fibrotic scleroderma lesions are associated with tissue retraction and increased production of extracellular matrix macromolecules, these data confirm the potential value of IFN-gamma for the treatment of scleroderma and other fibrotic diseases.
Serpier
H
H
Laboratoire de Biochimie, CNRS URA 610, Faculté de Médecine, Reims, France.
Gillery
P
P
Polette
M
M
Clavel
C
C
Birembaut
P
P
Kalis
B
B
Cariou
R
R
Maquart
F X
FX
D000328:Adult; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012595:Scleroderma, Systemic / Q000503:physiopathology / Q000628:therapy*
D016326:Extracellular Matrix Proteins; D011994:Recombinant Proteins; D007371:Interferon-gamma; D003094:Collagen
Modulation de l'organisation de la matrice extracellulaire et de la production de collagène par l'interféron gamma dans des cultures tridimensionnelles de fibroblastes normaux et sclérodermiques.