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Interleukin-4 inhibits the lipopolysaccharide-induced expression of c- jun and c-fos messenger RNA and activator protein-1 binding activity in human monocytes

WH Dokter, MT Esselink, MR Halie and E Vellenga

Department of Medicine, University of Groningen, The Netherlands.

We studied the effect of interleukin-4 (IL-4) on the lipopolysaccharide (LPS) induction of two immediate early genes c-fos and c-jun. These genes encode proteins that form the dimeric complex activator protein-1 (AP-1), which is active as a transcriptional factor. Maximal accumulation of either c-fos and c-jun messenger RNA (mRNA) occurred 30 minutes after LPS addition. When cells were treated with IL-4 for 5 hours before LPS activation, both the c-fos and the c-jun mRNA expression was decreased. The inhibition of c-fos and c-jun expression by IL-4 in LPS-treated cells was shown to be due to a lower transcription rate of the c-fos and c-jun genes. IL-4 did not affect the stability of the c-fos and c-jun transcripts. Finally, using electrophoretic mobility shift assays, evidence was obtained that IL-4 inhibits LPS-induced expression of AP-1 protein. These data indicate that IL-4 suppresses the induction of transcription factors in human activated monocytes.

Volume 81, Issue 2, pp. 337-343, 01/15/1993
Copyright © 1993 by The American Society of Hematology


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