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倍他米松-17-戊酸酯和异维A酸对转化生长因子-β的差异调节作用:皮质类固醇降低而异维A酸增加抽吸水疱液中转化生长因子-β的水平。

Differential modulation of transforming growth factor-beta by betamethasone-17- valerate and isotretinoin: corticosteroid decreases and isotretinoin increases the level of transforming growth factor-beta in suction blister fluid.

作者信息

Leivo T, Arjomaa P, Oivula J, Vesterinen M, Kiistala U, Autio P, Oikarinen A

机构信息

Department of Dermatology, University of Oulu and Oulu University Hospital, Oulu, Finland.

出版信息

Skin Pharmacol Appl Skin Physiol. 2000 May-Aug;13(3-4):150-6. doi: 10.1159/000029920.

Abstract

Retinoids and glucocorticoids are known to have a potential to modulate the expression of transforming growth factor-beta (TGF-beta). We investigated the effect of oral isotretinoin (13-cis-retinoic acid) on the expression of two distinct isoforms of TGF-beta, TGF-beta1 and TGF-beta2, in suction blister fluid and serum in acne patients. We also investigated the effect of topical glucocorticoid (betamethasone-17-valerate) and age on suction blister fluid TGF-beta1 in healthy volunteers. Six weeks of isotretinoin treatment caused a statistically significant 19% increase in suction blister fluid TGF-beta1. The suction blister fluid TGF-beta2 level remained below the sensitivity level of the immunoassay in many cases. Isotretinoin did not affect the serum TGF-beta1 or TGF-beta2 level. Betamethasone-17-valerate pretreatment for 3 days twice a day caused a statistically significant 17% decrease in suction blister fluid TGF-beta1. The active form of TGF-beta1 represented 5% of the total TGF-beta1 in suction blister fluid. Our diffusion calculations suggest that all TGF-beta1 and TGF-beta2 detected in suction blister fluid have diffused from systemic circulation. The increase in suction blister fluid TGF-beta1 after isotretinoin treatment seems to be of local origin, while the decrease in suction blister fluid TGF-beta1 after glucocorticoid pretreatment seems to be due to glucocorticoid-induced vasoconstriction resulting in decreased diffusion of TGF-beta1 from the circulation. Modulation of local interstitial fluid TGF-beta1 concentration may be one mechanism by which isotretinoin and glucocorticoids mediate their effects in skin.

摘要

已知维甲酸类药物和糖皮质激素具有调节转化生长因子-β(TGF-β)表达的潜力。我们研究了口服异维甲酸(13-顺式维甲酸)对痤疮患者水疱抽吸液和血清中两种不同亚型的TGF-β,即TGF-β1和TGF-β2表达的影响。我们还研究了局部应用糖皮质激素(倍他米松-17-戊酸酯)和年龄对健康志愿者水疱抽吸液中TGF-β1的影响。异维甲酸治疗六周后,水疱抽吸液中的TGF-β1有统计学意义地升高了19%。在许多情况下,水疱抽吸液中的TGF-β2水平仍低于免疫测定的灵敏度水平。异维甲酸不影响血清中的TGF-β1或TGF-β2水平。每天两次,连续3天进行倍他米松-17-戊酸酯预处理,导致水疱抽吸液中的TGF-β1有统计学意义地降低了17%。TGF-β1的活性形式占水疱抽吸液中总TGF-β1的5%。我们的扩散计算表明,水疱抽吸液中检测到的所有TGF-β1和TGF-β2均从体循环中扩散而来。异维甲酸治疗后水疱抽吸液中TGF-β1的增加似乎源于局部,而糖皮质激素预处理后水疱抽吸液中TGF-β1的降低似乎是由于糖皮质激素诱导的血管收缩导致TGF-β1从循环中的扩散减少。调节局部组织间液中TGF-β1的浓度可能是异维甲酸和糖皮质激素在皮肤中介导其作用的一种机制。

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