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Title: Cyclosporin A decreases human macrophage interleukin-6 synthesis at post-transcriptional level
Authors: Losa García, Juan E.
Rodríguez López, Ana M.
Martín de Cabo, María Rosa
Mateos Rodríguez, Fernando
Pérez Losada, Jesús
González Sarmiento, Rogelio
Jiménez López, Antonio
Pérez Arellano, José Luis 
Keywords: Necrosis-Factor-Alpha
Cell-Line U937
Phorbol-Myristate Acetate
Messenger-Rna, et al
Issue Date: 1999
Publisher: 0962-9351
Journal: Mediators of Inflammation 
Abstract: 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.
ISSN: 0962-9351
DOI: 10.1080/09629359990423
Source: Mediators of Inflammation[ISSN 0962-9351],v. 8, p. 253-259
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