钙调神经磷酸酶以及环孢素和他克莫司的生物学效应。

Calcineurin and the biological effect of cyclosporine and tacrolimus.

作者信息

Halloran P F, Kung L, Noujaim J

机构信息

Division of Nephrology and Immunology, University of Alberta, Edmonton, Canada.

出版信息

Transplant Proc. 1998 Aug;30(5):2167-70. doi: 10.1016/s0041-1345(98)00577-6.

DOI:10.1016/s0041-1345(98)00577-6

PMID:9723430

Abstract

The mechanism of the immunosuppressive effect of CyA and FK 506 can be monitored in vivo in humans. The picture emerging is of a close relationship between drug concentrations and CN inhibition. But many puzzles of the drugs remain. What is the role of CyA in the activation of transforming growth factor-beta (TGF-beta), particularly in relationship to nephrotoxicity and fibrogenesis? How important are the anti-inflammatory (non T) effects of CyA, and which cells do they operate in? Are there effects of CyA and FK 506 all attributable to CN inhibition, and how much of them are mediated through the NFATC family of transcription factors? Finally, it would be useful to know what the inhibitory effects of CyA are on tolerance and negative regulatory events.

摘要

环孢素A（CyA）和他克莫司（FK 506）免疫抑制作用的机制可在人体中进行体内监测。目前呈现出的情况是药物浓度与钙调神经磷酸酶（CN）抑制之间存在密切关系。但这些药物仍存在许多谜团。CyA在转化生长因子-β（TGF-β）激活中起什么作用，特别是与肾毒性和纤维化形成的关系？CyA的抗炎（非T细胞）作用有多重要，它们作用于哪些细胞？CyA和FK 506的作用是否都归因于CN抑制，其中有多少是通过NFATC转录因子家族介导的？最后，了解CyA对耐受性和负调节事件的抑制作用将是很有用的。