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Is cyclophilin involved in the immunosuppressive and nephrotoxic mechanism of action of cyclosporin A? by N H Sigal; F Dumont; P Durette; J J Siekierka; L Peterson; D H Rich; B E Dunlap; M J Staruch; M R Melino; S L Koprak is a Immunology and Microbiology article available to read on EtoBox.
What is Is cyclophilin involved in the immunosuppressive and nephrotoxic mechanism of action of cyclosporin A? about?
In this report we have approached two questions relating to the mechanism of action of cyclosporin A (CsA). First, we address whether the major cytosolic protein for CsA, cyclophilin, is directly involved in mediating the immunosuppressive activity of this drug, and, in particular, whether inhibition of this protein's peptidyl-prolyl cis- trans isomerase (PPIase) activity results in inhibition of murine T cell activation. Second, we ask whether the nephrotoxicity observed with CsA is related to inhibition of PPIase-dependent pathways in cells other than lymphocytes. Using a series of 61 cyclosporin analogues, we generally found a good correlation between cyclophilin binding and immunosuppressive activity for the majority of analogues analyzed. However, a number of compounds of distinct structural classes were found that could interact with cyclophilin but were much less immunosuppressive than expected. The inability of these analogues to inhibit lymphocyte activation could not be explained by their failure to enter the cell and bind to cyclophilin under the conditions used in the cellular assays. Surprisingly, a nonimmunosuppressive analogue, MeAla-6, which bound well to cyclophili
Who reads Is cyclophilin involved in the immunosuppressive and nephrotoxic mechanism of action of cyclosporin A??
It is typically read by researchers, students, and practitioners in Immunology and Microbiology.
- Author
- N H Sigal; F Dumont; P Durette; J J Siekierka; L Peterson; D H Rich; B E Dunlap; M J Staruch; M R Melino; S L Koprak
- Publisher
- The Rockefeller University Press
- Published
- 1991
- Language
- EN
- Field
- Immunology and Microbiology (Life Sciences)