Stimulation of sulphated glycosaminoglycan and decorin production in adult dermal fibroblasts by recombinant human interleukin-4.
Interleukin-4 (IL-4) is a pleiotropic cytokine expressed by inflammatory cells. Previous work from our laboratory has shown that it stimulates collagen synthesis in fibroblasts. Here we report the effects of recombinant human IL-4 on glycosaminoglycan (GAG) and proteoglycan synthesis in normal dermal fibroblasts from adult donors. IL-4 (10 and 100 units/ml) induced a dose-dependent increase of [3H]glucosamine and [35S]sulphate incorporation into total GAGs. The analysis of the different GAG fractions indicated the enhanced synthesis of dermatan/chondroitin sulphates. IL-4 had no effect on hyaluronan synthesis. The increase of sulphated GAG synthesis was correlated with an increase of proteoglycans in the culture medium. Decorin was identified as the major chondroitin/dermatan sulphate-containing proteoglycan in the culture medium of fibroblasts. Its synthesis was strongly stimulated by IL-4. Both the core-protein synthesis and mRNA expression were enhanced, indicating that the cytokine acted, at least in part, at the pre-translational level. These results indicate that IL-4 is able to modulate not only collagen, but also proteoglycan, production by human fibroblasts. Their implications in physiopathological processes such as wound healing or fibrosis is suggested.
Wegrowski
Y
Y
Laboratoire de Biochimie (CNRS ER 084), Faculté de Médecine, France.
Paltot
V
V
Gillery
P
P
Kalis
B
B
Randoux
A
A
Maquart
F X
FX
D000328:Adult; D001483:Base Sequence; D002478:Cells, Cultured; D002648:Child; D003470:Culture Media; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005110:Extracellular Space / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011509:Proteoglycans / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D013268:Stimulation, Chemical; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014158:Transcription, Genetic
D003470:Culture Media; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D011509:Proteoglycans; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013431:Sulfates; D013462:Sulfur Radioisotopes; D015847:Interleukin-4; C013786:A73025