Facilitation of apoptosis by cyclosporins A and H, but not FK506 in mouse bronchial eosinophils

European Journal of Pharmacology
K KitagakiT Totsuka

Abstract

This study was undertaken to clarify whether or not binding to cyclophilin is a prerequisite for cyclosporin A-induced modulation of apoptotic cell death in eosinophils. Eosinophils were isolated from bronchoalveolar lavage fluid of mice challenged with inhaled allergen after sensitization. Apoptosis was determined by analysing the DNA content. At 72 h, 99% of the cells had died without addition of cytokines, whereas 55-60% of the cells survived in the presence of 10 U/ml recombinant murine interleukin 5 or recombinant murine granulocyte macrophage-colony stimulation factor (GM-CSF). Apoptotic cell death at 72 h in the presence of 10 U/ml interleukin 5 was increased by addition of cyclosporin H, an analogue of cyclosporin A without cyclophilin binding activity, in a concentration-dependent (0.3 to 3 microM) manner. The increase in apoptosis elicited by cyclosporin A and cyclosporin H took place also in the presence of 10 U/ml GM-CSF but to a lesser extent. There was a significant augmentation of apoptosis in eosinophils cultured in the presence of each cytokine for 72 h or longer. Tacrolimus (FK506) failed to augment apoptotic cell death. Thus, it is unlikely that binding of cyclosporin A to cyclophilin accounts for the increas...Continue Reading

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Citations

May 7, 2003·The Journal of Steroid Biochemistry and Molecular Biology·Sanjay ChauhanRoger L Miesfeld
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·J P LeeR P Roos
Nov 24, 1999·Critical Reviews in Clinical Laboratory Sciences·G M Walsh
Nov 4, 2000·Expert Opinion on Investigational Drugs·J K Weltman, A S Karim
Jul 14, 2010·Orthodontics & Craniofacial Research·R L SantosM M G de Souza
Jul 10, 2003·Chemical Reviews·Christophe Dugave, Luc Demange

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