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 derma...

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Bibliographic Details
Published in:	Biochemical journal Vol. 307 ( Pt 3); no. 3; pp. 673 - 678
Main Authors:	Wegrowski, Y, Paltot, V, Gillery, P, Kalis, B, Randoux, A, Maquart, F X
Format:	Journal Article
Language:	English
Published:	England 01-05-1995
Subjects:	Adult Base Sequence Cells, Cultured Child Culture Media Decorin Extracellular Matrix Proteins Extracellular Space - metabolism Fibroblasts - drug effects Fibroblasts - metabolism Glycosaminoglycans - biosynthesis Humans Interleukin-4 - pharmacology Molecular Sequence Data Polymerase Chain Reaction Proteoglycans - biosynthesis Proteoglycans - genetics Proteoglycans - metabolism Recombinant Proteins - pharmacology RNA, Messenger - genetics RNA, Messenger - metabolism Skin - cytology Skin - drug effects Skin - metabolism Stimulation, Chemical Sulfates - metabolism Sulfur Radioisotopes Transcription, Genetic
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0264-6021 1470-8728
DOI:	10.1042/bj3070673