Mediators of Inflammation

Mediators of Inflammation / 1999 / Article

Open Access

Volume 8 |Article ID 193147 |

Juan E. Losa García, Ana M. Rodríguez López, María Rosa Martín De Cabo, Fernando Mateos Rodríguez, Jesús Pérez Losada, Rogelio González Sarmiento, Antonio Jiménez López, José Luis Pérez Arellano, "Cyclosporin A Decreases Human Macrophage Interleukin-6 Synthesis at Post-Transcriptional Level ", Mediators of Inflammation, vol. 8, Article ID 193147, 7 pages, 1999.

Cyclosporin A Decreases Human Macrophage Interleukin-6 Synthesis at Post-Transcriptional Level


In addition to its well-established effect on T cells, cyclosporin A (CsA) also inhibits inflammatory cytokine production by macrophages. However, little is known about the mechanism of action of CsA on macrophage cytokine production. We measured the effect of CsA on basal and phorbol-myristate-acetate (PMA)-stimulated production of interleukin-6 using the human monocyte cell line U937 differentiated with dimethylsulfoxide (DMSO). Interleukin-6 levels were measured in supernatant and cell lysates using specific enzyme-linked immunosorbent assays. We found that CsA decreases not only IL-6 release but also cytokine synthesis. The concentration of CsA used did not affect either cell viability or proliferation. Three possibilities may be advanced to explain the CsA-due decrease in IL-6 production by macrophages: (a) inhibition of the synthesis of an early common regulatory protein, (b) inhibition of cytokine gene transcription, or (c) modulation of post-transcriptional events. The first possibility was tested by measuring the effect of cycloheximide on the experimental system during the first 3 hours of culture. Although cycloheximide decreased total cytokine synthesis, the pattern of cytokine modulation by CsA persisted. These data suggest that CsA-mediated macrophage cytokine inhibition is not mediated by an early common regulatory protein. To further explore the inhibition mechanism, we measured IL-6 mRNA levels by Northern blot. IL-6 mRNA levels were unaffected by CsA both in resting and PMA-stimulated cells. We conclude that in human macrophages CsA diminishes IL-6 production at post-transcriptional level.

Copyright © 1999 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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