Department of Biotechnology, Central Leather Research Institute, Adyar, Chennai, India.
Rheumatol Int. 2012 Oct;32(10):3181-8. doi: 10.1007/s00296-011-2146-x. Epub 2011 Sep 30.
Sexual dimorphism is a well-established phenomenon in rheumatoid arthritis, with women exhibiting higher disease severity. Understanding the role of sex hormones using in vivo animal models is limited due to the systemic effects as well as the difficulty in exploring different dose combinations of the hormones simultaneously. However, cell culture systems pose ideal systems for exploring different combinations and concentrations of the hormones simultaneously. In this study, the procedure for isolation of arthritic fibroblasts was standardized using a combination of collagenase and trypsin based on maximal yield and viability after employing different enzymatic disaggregation procedures. The cultured synovial fibroblasts from arthritic rats did not differ significantly from normal rat fibroblasts in terms of proliferation or secretion of inflammatory mediators. Stimulation of fibroblasts with TNF-α was standardized and TNF-α stimulated rat arthritic synovial fibroblasts exhibited an ideal in vitro system for screening antiinflammatory molecules. The effects of physiological and pharmacological concentrations of testosterone, estrogen and progesterone were studied on TNF-α induced cellular damage in rat arthritic synovial fibroblasts. The results showed that estrogen and testosterone exerted antiinflammatory effects on rat arthritic synovial fibroblasts at physiological and pharmacological concentrations. However, there was no significant difference in the effects between physiological and pharmacological concentrations. Progesterone independently did not show any protective effects. In combination with physiological concentrations of estrogen, progesterone abrogated estrogen's protective effect but it exhibited protection in combination with pharmacological concentrations of estrogen.
性别二态性是类风湿关节炎中一个既定的现象，女性表现出更高的疾病严重程度。由于激素的全身作用以及同时探索不同剂量组合的困难，使用体内动物模型来理解性激素的作用是有限的。然而，细胞培养系统是同时探索不同激素组合和浓度的理想系统。在这项研究中，通过使用基于胶原酶和胰蛋白酶的组合，根据不同酶解程序后的最大产量和活力，对关节炎成纤维细胞的分离程序进行了标准化。从关节炎大鼠培养的滑膜成纤维细胞在增殖或炎症介质分泌方面与正常大鼠成纤维细胞没有显著差异。使用 TNF-α 刺激成纤维细胞并进行了标准化，并且 TNF-α 刺激的大鼠关节炎滑膜成纤维细胞表现出了用于筛选抗炎分子的理想体外系统。研究了生理和药理浓度的睾酮、雌激素和孕激素对 TNF-α诱导的大鼠关节炎滑膜成纤维细胞细胞损伤的影响。结果表明，雌激素和睾酮在生理和药理浓度下对大鼠关节炎滑膜成纤维细胞发挥抗炎作用。然而，在生理和药理浓度之间，作用没有显著差异。孕激素本身没有表现出任何保护作用。与生理浓度的雌激素联合使用时，孕激素消除了雌激素的保护作用，但与药理浓度的雌激素联合使用时则表现出保护作用。
