O'Byrne E M, Schroder H C, Stefano C, Goldberg R L
Research Department Pharmaceuticals Division, CIBA-GEIGY Corporation Ardsley, NY 10502.
Agents Actions. 1987 Aug;21(3-4):341-4. doi: 10.1007/BF01966510.
Catabolin/interleukin-1 effects on metabolism were studied in bovine nasal cartilage organ culture and articular chondrocyte cell culture. Keratan sulfate (KS) and hyaluronic acid (HA) were determined by an ELISA; prostaglandin E2 by RIA, sulfated glycosaminoglycan using dimethylmethylene blue and proliferation by incorporation of tritiated thymidine. Gel filtration of untreated 4-day organ culture media indicated that large sulfated and KS-containing proteoglycans were released and eluted in the void volume. Catabolin/interleukin-1 increased release of sulfated glycosaminoglycans and these were of lower molecular weight with an altered distribution of KS. Catabolin/interleukin-1 treatment of chondrocytes caused a decrease in KS production and proliferation but an increase in HA and in prostaglanding E2 production. Alterations of the chondrocyte metabolism by catabolin/interleukin-1 causing proteoglycan matrix degradation and modulation of chondrocyte glycosaminoglycan biosynthesis and proliferation may play a role in cartilage erosion and failure to repair in arthritic diseases.
在牛鼻软骨器官培养和关节软骨细胞培养中研究了分解代谢素/白细胞介素-1对代谢的影响。通过酶联免疫吸附测定法(ELISA)测定硫酸角质素(KS)和透明质酸(HA);通过放射免疫分析法(RIA)测定前列腺素E2,使用二甲基亚甲基蓝测定硫酸化糖胺聚糖,并通过掺入氚标记的胸腺嘧啶核苷来测定增殖情况。对未经处理的4天器官培养基进行凝胶过滤表明,大的硫酸化且含KS的蛋白聚糖被释放并在空体积中洗脱。分解代谢素/白细胞介素-1增加了硫酸化糖胺聚糖的释放,且这些糖胺聚糖分子量较低,KS的分布也发生了改变。分解代谢素/白细胞介素-1处理软骨细胞导致KS产生和增殖减少,但HA和前列腺素E2产生增加。分解代谢素/白细胞介素-1引起软骨细胞代谢改变,导致蛋白聚糖基质降解以及软骨细胞糖胺聚糖生物合成和增殖的调节,这可能在关节炎疾病的软骨侵蚀和修复失败中起作用。