Zettersten E, Man M Q, Sato J, Denda M, Farrell A, Ghadially R, Williams M L, Feingold K R, Elias P M
Veterans Affairs Medical Center, and Department of Dermatology, University of California, San Francisco 94121, USA.
J Invest Dermatol. 1998 Nov;111(5):784-90. doi: 10.1046/j.1523-1747.1998.00386.x.
Cholesterol sulfate is a multifunctional sterol metabolite, produced in large amounts in squamous keratinizing epithelia. Because patients with recessive x-linked ichthyosis display not only a 10-fold increase in cholesterol sulfate, but also a 50% reduction in cholesterol, we assessed here whether cholesterol sulfate accumulation and/or cholesterol deficiency produce abnormal barrier function in recessive x-linked ichthyosis. Patients with recessive x-linked ichthyosis display both an abnormal barrier under basal conditions, and a delay in barrier recovery after acute perturbation, which correlate with minor abnormalities in membrane structure and extensive lamellar-phase separation. Moreover, both the functional and the structural abnormalities were corrected by topical cholesterol. Yet, topical cholesterol sulfate produced both a barrier abnormality in intact skin and extracellular abnormalities in isolated stratum corneum, effects largely reversed by coapplications of cholesterol. Together, these results suggest that cholesterol sulfate accumulation rather than cholesterol deficiency is responsible for the barrier abnormality. Despite the apparent importance of cholesterol sulfate-to-cholesterol processing for normal barrier homeostasis, neither steroid sulfatase activity nor mRNA levels are upregulated following acute perturbations. These results demonstrate both a potential role for cholesterol sulfate-to-cholesterol processing in normal permeability barrier homeostasis, and that basal levels of steroid sulfatase are sufficient to accommodate acute insults to the permeability barrier.
硫酸胆固醇是一种多功能的甾醇代谢产物，在鳞状角质化上皮中大量产生。由于隐性X连锁鱼鳞病患者不仅硫酸胆固醇增加了10倍，而且胆固醇减少了50%，我们在此评估硫酸胆固醇的积累和/或胆固醇缺乏是否会在隐性X连锁鱼鳞病中产生异常的屏障功能。隐性X连锁鱼鳞病患者在基础条件下表现出异常的屏障功能，并且在急性扰动后屏障恢复延迟，这与膜结构的轻微异常和广泛的片层相分离相关。此外，局部应用胆固醇可纠正功能和结构异常。然而，局部应用硫酸胆固醇在完整皮肤中产生屏障异常，在分离的角质层中产生细胞外异常，这些作用在同时应用胆固醇后大部分得到逆转。总之，这些结果表明，屏障异常是由硫酸胆固醇的积累而非胆固醇缺乏引起的。尽管硫酸胆固醇向胆固醇的转化对于正常的屏障稳态显然很重要，但在急性扰动后，类固醇硫酸酯酶活性和mRNA水平均未上调。这些结果表明，硫酸胆固醇向胆固醇的转化在正常的通透性屏障稳态中具有潜在作用，并且类固醇硫酸酯酶的基础水平足以适应对通透性屏障的急性损伤。
