Wegrowski Y, Paltot V, Gillery P, Kalis B, Randoux A, Maquart F X
Laboratoire de Biochimie (CNRS ER 084), Faculté de Médecine, France.
Biochem J. 1995 May 1;307 ( Pt 3)(Pt 3):673-8. doi: 10.1042/bj3070673.
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.
白细胞介素-4（IL-4）是一种由炎症细胞表达的多效性细胞因子。我们实验室之前的研究表明，它能刺激成纤维细胞中的胶原蛋白合成。在此，我们报告重组人IL-4对成年供体正常皮肤成纤维细胞中糖胺聚糖（GAG）和蛋白聚糖合成的影响。IL-4（10和100单位/毫升）诱导[3H]葡萄糖胺和[35S]硫酸盐掺入总GAGs的量呈剂量依赖性增加。对不同GAG组分的分析表明，硫酸皮肤素/硫酸软骨素的合成增强。IL-4对透明质酸合成没有影响。硫酸化GAG合成的增加与培养基中蛋白聚糖的增加相关。核心蛋白聚糖被鉴定为成纤维细胞培养基中主要的含硫酸软骨素/硫酸皮肤素的蛋白聚糖。其合成受到IL-4的强烈刺激。核心蛋白合成和mRNA表达均增强，表明该细胞因子至少部分在翻译前水平起作用。这些结果表明，IL-4不仅能够调节人成纤维细胞的胶原蛋白产生，还能调节蛋白聚糖的产生。提示了它们在伤口愈合或纤维化等生理病理过程中的意义。
