Lyons-Giordano B, Kefalides N A, Brinker J M, Pratta M A, Arner E C
DuPont Merck Pharmaceutical Company, Wilmington, Delaware 19880.
Exp Cell Res. 1991 Aug;195(2):462-7. doi: 10.1016/0014-4827(91)90397-d.
Studies to evaluate the effects of recombinant interleukin-1 beta (IL-1) on the expression of matrix proteins by rabbit articular chondrocytes were conducted. Chondrocytes expressed high levels of message for thrombospondin (Tsp) and fibronectin (Fn). RNA slot-blot analysis demonstrated that treatment of the cultures with IL-1 (100 ng/ml) for 24 h caused a 70% suppression of their steady-state Tsp mRNA levels whereas those of Fn were not affected. Steady-state mRNA levels for the intracellular protein, actin, were not modulated by treatment with IL-1. The suppression of Tsp mRNA levels by IL-1 (100 ng/ml) was maximal by 4 h and was concentration dependent; half-maximal suppression was estimated to require 0.12 ng/ml IL-1. Cycloheximide treatment enhanced Tsp mRNA levels, but did not modulate IL-1 suppression of Tsp mRNA. Using pulse-labeling and immunoprecipitation techniques, we found that IL-1 suppression of Tsp mRNA levels was reflected in a coordinate inhibition of Tsp protein synthesis. Chondrocyte synthesis of Fn was not affected by IL-1. These data suggest that IL-1 specifically regulates chondrocyte expression of Tsp at least in part by decreasing the amount of Tsp mRNA available for translation.
开展了评估重组白细胞介素 -1β（IL -1）对兔关节软骨细胞基质蛋白表达影响的研究。软骨细胞表达高水平的血小板反应蛋白（Tsp）和纤连蛋白（Fn）的信息。RNA 斑点印迹分析表明，用 IL -1（100 ng/ml）处理培养物 24 小时导致其稳态 Tsp mRNA 水平抑制 70%，而 Fn 的水平未受影响。细胞内蛋白肌动蛋白的稳态 mRNA 水平不受 IL -1 处理的调节。IL -1（100 ng/ml）对 Tsp mRNA 水平的抑制在 4 小时时最大且呈浓度依赖性；估计半最大抑制需要 0.12 ng/ml 的 IL -1。放线菌酮处理可提高 Tsp mRNA 水平，但不调节 IL -1 对 Tsp mRNA 的抑制。使用脉冲标记和免疫沉淀技术，我们发现 IL -1 对 Tsp mRNA 水平的抑制反映在对 Tsp 蛋白合成的协同抑制上。IL -1 不影响软骨细胞 Fn 的合成。这些数据表明，IL -1 至少部分地通过减少可用于翻译的 Tsp mRNA 的量来特异性调节软骨细胞 Tsp 的表达。
