Granulocyte-macrophage colony-stimulating factor regulation in murine T cells and its relation to cyclosporin A.
The coordinated expression of the hematopoietic growth factors, interleukin 3 (IL3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in activated T cells suggests common synthetic pathways. However, cyclosporin A (CsA) appears to differentially effect the synthesis of these two lymphokines. When the supernatants from the concanavalin A-stimulated thymoma EL-4 or the T-cell hybrid 2B4 were assayed on the GM-CSF/IL3-dependent PT-18 and on the IL3-dependent DA-1 cell lines, IL3 activity could not be detected following CsA treatment, but substantial growth activity, which was identified as GM-CSF, was observed on the PT-18 cell line. CsA did not affect the kinetics of GM-CSF release, but inhibited the release of IL3 over a period of 40 h after the cells were stimulated and treated with CsA. In addition, CsA could be added up to 1 h after stimulation of the cells without affecting GM-CSF activity but inhibiting completely the IL3 activity. To substantiate the inability of CsA to inhibit GM-CSF activity, GM-CSF gene expression was evaluated. By Northern analysis GM-CSF mRNA was not inhibited by doses of CsA up to 1 microgram/ml. The data reveal that CsA can dissociate between the production of IL3 and GM-CSF, suggesting that these two CSFs are regulated by different mechanisms.
D000818:Animals; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000096:biosynthesis* / Q000235:genetics / Q000493:pharmacokinetics; D003524:Cyclosporins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics / Q000493:pharmacokinetics; D007377:Interleukin-3 / Q000096:biosynthesis / Q000493:pharmacokinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D012333:RNA, Messenger / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D003524:Cyclosporins; D006133:Growth Substances; D007377:Interleukin-3; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate