Browning J L, Ward M P, Wallner B P, Pepinsky R B
Department of Cell Biology, Biogen, Inc., Cambridge, MA 02142.
Prog Clin Biol Res. 1990;349:27-45.
Lipocortin-1 protein synthesis in resting monocytes is under the control of glucocorticoid steroids. This induction occurs at reasonable dexamethasone concentrations, may require concomitant synthesis of transcriptional factors, appears to be cell type specific, and has been observed only in primary tissues in our hands. Variability in the magnitude of the induction suggests that the regulation is complex, involving either additional factors or particular differentiation states. In addition to the induction of intracellular lipocortin-1, steroids cause the appearance of labelled lipocortin-1 on the outer surface of the cells. Whether cell breakage can account for this effect is unclear. Considerable microheterogeneity was found in preparations of recombinant-lipocortin-1. Aspects of N-terminal post-translational processing, N-terminal proteolysis, conformational states and the existence of an air-denatured form lacking alpha-helical structure contributed to this heterogeneity. We believe that these aspects are responsible for the variable biological potency of different preparations. It remains unclear whether this protein actually plays a physiological role in the regulation of the inflammatory response or achieves its effects through membrane binding and subsequent non-physiological perturbation of the cells.
静息单核细胞中脂皮质素-1的蛋白质合成受糖皮质激素的控制。这种诱导作用在合理的地塞米松浓度下发生，可能需要转录因子的同时合成，似乎具有细胞类型特异性，并且在我们的研究中仅在原代组织中观察到。诱导程度的变异性表明该调节是复杂的，涉及其他因素或特定的分化状态。除了诱导细胞内脂皮质素-1外，类固醇还会导致细胞外表面出现标记的脂皮质素-1。细胞破碎是否能解释这种效应尚不清楚。在重组脂皮质素-1制剂中发现了相当大的微观异质性。N端翻译后加工、N端蛋白水解、构象状态以及缺乏α-螺旋结构的空气变性形式的存在等方面导致了这种异质性。我们认为这些方面是不同制剂生物学活性可变的原因。目前尚不清楚这种蛋白质是否真的在炎症反应调节中发挥生理作用，或者是通过膜结合以及随后对细胞的非生理性扰动来实现其作用。
