Production of collagenase and inhibitor (TIMP) by normal, rheumatoid and osteoarthritic synovium in vitro: effects of hydrocortisone and indomethacin.
Production of collagenase and inhibitor (TIMP) by normal, rheumatoid and osteoarthritic synovium in vitro: effects of hydrocortisone and indomethacin.
复制标题
正常、类风湿和骨关节炎滑膜体外产生胶原酶和抑制剂（TIMP）：氢化可的松和吲哚美辛的作用。
作者：
M. McGuire;G. Murphy;J. Reynolds;R. Russell
1.比较培养中的两个正常、三个类风湿和两个骨关节炎滑膜标本产生的潜在和活性胶原酶以及胶原酶抑制剂（TIMP）的量。正常滑液产生TIMP，但几乎没有潜伏酶。类风湿性滑膜产生的总胶原酶活性水平高于正常水平，其中在一份样品中高达 50% 以活性形式存在于培养基中，而没有检测到 TIMP 引起的特异性抑制活性。骨关节炎滑液产生的胶原酶和 TIMP 的量变化较大，似乎反映了开始培养时组织的炎症程度。 2.当存在氢化可的松时，正常、类风湿和骨关节炎滑液的培养基中TIMP的浓度通常较高。相应地，总胶原酶的量减少。氢化可的松以剂量依赖性方式抑制前列腺素 E (PGE) 的产生。 3.吲哚美辛对类风湿和骨关节炎滑液产生TIMP没有一致的影响，尽管它倾向于抑制胶原酶的产生。吲哚美辛可抑制正常滑液产生 TIMP。当存在吲哚美辛时，在介质中未检测到 PGE。 4. 这些结果与之前的动物研究结果一致，我们得出结论，胶原酶和 TIMP 产生之间的平衡对于确定关节炎破坏过程的程度可能至关重要。氢化可的松抑制胶原酶产生、增加游离 TIMP 浓度以及抑制前列腺素合成的能力，可以部分解释该药物如何对类风湿性关节炎患者发挥治疗作用。
1. The amounts of latent and active collagenase and of collagenase inhibitor (TIMP) produced by two normal, three rheumatoid and two osteoarthritic synovial specimens in culture were compared. Normal synovia produced TIMP, but little latent enzyme. Rheumatoid synovia produced higher levels of total collagenase activity than normal, of which up to 50% in one sample was present in the medium in an active form, whereas no specific inhibitory activity due to TIMP was detectable. The amounts of collagenase and TIMP produced by osteoarthritic synovia were more variable and appeared to reflect the degree of inflammation in the tissue at the time of initiating the cultures. 2. Concentrations of TIMP were usually higher in the culture media of normal, rheumatoid and osteoarthritic synovia when hydrocortisone was present. Correspondingly, amounts of total collagenase were reduced. Production of prostaglandin E (PGE) were inhibited in a dose-dependent manner by hydrocortisone. 3. Indomethacin had no consistent effect on the production of TIMP by rheumatoid and osteoarthritic synovia, although it tended to depress production of collagenase. The production of TIMP by normal synovia was depressed by indomethacin. No PGE was detectable in the media when indomethacin was present. 4. These results are consistent with those from previous animal studies, and we conclude that the balance between production of collagenase and TIMP may be critical in determining the extent of the destructive processes in arthritis. The ability of hydrocortisone to suppress production of collagenase and to increase free TIMP concentration, as well as to inhibit synthesis of prostaglandin, may explain in part how the drug exerts its therapeutic effects in patients with rheumatoid arthritis.