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

Abstract

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.

Interleukin‐4 Suppresses IL‐17–Induced Expression of Matrix Metalloproteinase‐3 in Human Gingival Fibroblasts

“…63 There is also some evidence that NF-κB may play a role. [55][56][57] IL-4 has been shown to affect gene expression by interfering with the DNA binding activity of AP-1 58,59 and NF-κB [60][61][62] in other systems; however, our results tion of MMP-3. Inhibition of prostaglandin synthesis by indomethacin or other inhibitors of cyclooxygenase has been shown to both augment 50 and inhibit 47,69 MMP-3 expression, as has exogenous addition of PGE 2 46,48-50 and alterations in levels of cAMP.…”

“…Transcription factor AP-1 is an important factor in the regulation of the MMP-3 gene [51][52][53][54] and there is evidence that NF-κB may also play a role. [55][56][57] Since IL-4 has been shown in other systems to inhibit gene expression by interfering with AP-1 58,59 and NF-κB activation, [60][61][62] the effects of IL-4 on AP-1 and NF-κB DNA binding were investigated. Nuclear extracts were isolated from HGF cultures 1 hour after addition of IL-1 alone, IL-4 IL-4 inhibits IL-1 induction of MMP-3 mRNA in HGF.…”

Catecholamines potentiate LPS‐induced expression of MMP‐1 and MMP‐9 in human monocytes and in the human monocytic cell line U937: possible implications for peri‐ operative plaque instability

“…The stimulating effect of catecholamines on LPS-induced MMP-1 and MMP-9 expression was completely blocked by cycloheximide, indicating that it was dependent on de novo protein synthesis. The promoters of most MMPs including MMP-1 and MMP-9 contain consensus sites for AP-1, and it is known that LPS rapidly up-regulates c-Fos and c-Jun activities at early time points (21,28). To further investigate any role of transcription factor AP-1, we used an ELISA-based assay to measure DNA binding activity of c-Fos and c-Jun.…”

MUTZ‐3, a monocytic model cell line for interleukin‐4 and lipopolysaccharide studies

“…1 Interleukin-4 (IL-4) down-regulates CD14 2,3,4 and inhibits the LPS-induced expression of tumour necrosis factor-a (TNF-a), IL-1b and IL-6 mRNA as well as protein secretion in peripheral blood monocytes (PBMo). 5,6 In addition, IL-4 diminishes the LPS-induced binding activity of the transcription factor AP-1 7 and suppresses the activation of NF kB . 8 Both transcription factors bind to regulating target sequences in the promoters of the monocyte-related cytokine genes mentioned above.…”