Vance B A, Kowalski C G, Brinckerhoff C E
Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03756.
J Cell Biol. 1989 Jun;108(6):2037-43. doi: 10.1083/jcb.108.6.2037.
Two metalloproteinases, collagenase and stromelysin, are produced in large quantities by synovial fibroblasts in individuals with rheumatoid arthritis. These enzymes play a major role in the extensive destruction of connective tissue seen in this disease. In this study, we show that heat shock of monolayer cultures of rabbit synovial fibroblasts increases expression of mRNA for heat shock protein 70 (HSP-70), and for collagenase and stromelysin. We found that after heat shock for 1 h at 45 degrees C, the mRNA expression for HSP-70 peaks at 1 h and returns to control levels by 3 h. Collagenase and stromelysin mRNA expression is coordinate, reaching peak levels at 3 h and returning to control levels by 10 h. The increase in mRNA is paralleled by an increase in the corresponding protein in the culture medium. 3 h of heat shock at a lower temperature (42 degrees C) is also effective in inducing collagenase and stromelysin mRNAs. Concomitant treatment with phorbol myristate acetate (PMA; 10(-8) or 10(-9) M) and heat shock is not additive or synergistic. In addition, all-trans-retinoic acid, added just before heat shock, prevents the increase in mRNAs for collagenase and stromelysin. Our data suggest that heat shock may be an additional mechanism whereby collagenase and stromelysin are increased during rheumatoid arthritis and perhaps in other chronic inflammatory stress conditions.
在类风湿性关节炎患者中，滑膜成纤维细胞会大量产生两种金属蛋白酶，即胶原酶和基质溶解素。这些酶在该疾病中结缔组织的广泛破坏过程中起主要作用。在本研究中，我们发现对兔滑膜成纤维细胞单层培养物进行热休克处理可增加热休克蛋白70（HSP - 70）、胶原酶和基质溶解素的mRNA表达。我们发现，在45℃热休克1小时后，HSP - 70的mRNA表达在1小时达到峰值，并在3小时恢复到对照水平。胶原酶和基质溶解素的mRNA表达是协同的，在3小时达到峰值水平，并在10小时恢复到对照水平。mRNA的增加与培养基中相应蛋白质的增加平行。在较低温度（42℃）下进行3小时的热休克也能有效诱导胶原酶和基质溶解素的mRNA。用佛波酯肉豆蔻酸酯（PMA；10⁻⁸或10⁻⁹M）与热休克同时处理并无相加或协同作用。此外，在热休克前加入全反式维甲酸可阻止胶原酶和基质溶解素mRNA的增加。我们的数据表明，热休克可能是类风湿性关节炎以及其他慢性炎症应激条件下胶原酶和基质溶解素增加的另一种机制。
