Effect of retinoids on rheumatoid arthritis, a proliferative and invasive non-malignant disease.
Effect of retinoids on rheumatoid arthritis, a proliferative and invasive non-malignant disease.
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类维生素A对类风湿性关节炎（一种增殖性和侵袭性非恶性疾病）的影响。
DOI：
10.1002/9780470720943.ch12
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Wilder,RL
中科院分区：
文献类型：
--
作者：
Brinckerhoff,CE;Sheldon,LA;Benoit,MC;Burgess,DR;Wilder,RL
在类风湿性关节炎滑膜组织增生和破坏关节软骨，骨和肌腱。胶原酶是结缔组织降解的主要介质。这种酶由类风湿组织大量产生，其合成可被类维生素A抑制。然而，控制类维生素A抑制胶原酶产生的机制和可能控制滑膜细胞增殖的因素的知识是有限的。我们发现，转化生长因子与表皮生长因子、表皮生长因子单独和免疫干扰素的组合增加了培养的人和兔滑膜成纤维细胞的增殖。只有转化生长因子引起细胞聚集成类似于人类风湿组织原代培养物中所见的病灶。所有因子均能被类维生素A拮抗，但不能被糖皮质激素或吲哚美辛拮抗。向胶原酶产生细胞中加入维甲酸或糖皮质激素，24 h内可杂交的胶原酶mRNA减少50%。口服类维生素A给实验性关节炎大鼠减少临床疾病，而没有毒性，并抑制胶原酶合成的滑膜细胞从治疗的动物。类维生素A既具有抗增殖性又具有抗侵袭性。因此可能是治疗类风湿性关节炎的潜在治疗剂。
In rheumatoid arthritis synovial tissue proliferates and destroys articular cartilage, bone and tendons. Collagenase is a major mediator of the connective tissue degradation. This enzyme is produced in large quantities by rheumatoid tissue and its synthesis can be inhibited by retinoids. However, knowledge of mechanisms controlling retinoid inhibition of collagenase production and of factors possibly controlling synovial cell proliferation is limited. We found that transforming growth factor@ in combination with epidermal growth factor, epidermal growth factor alone and immune interferon increased proliferation of cultured human and rabbit synovial fibroblasts. Only transforming growth factor@ caused a piling up of cells into foci resembling those seen in primary cultures of human rheumatoid tissue, All the factors were antagonized by retinoids but not by glucocorticoids or indomethacin. Adding retinoids or glucocorticoids to collagenaseproducing cells decreased hybridizable collagenase mRNA by 50% within 24 h. Oral administration of retinoids to rats with experimental arthritis decreased clinical disease without toxicity, and inhibited collagenase synthesis by synovial cells taken from treated animals. Retinoids are both antiproliferative and anti-invasive. and therefore may be potential therapeutic agents in the treatment of rheumatoid arthritis.