2-Acetylaminofluorene inhibits interleukin-1 beta production in LPS-stimulated macrophages by blocking NF-kappa B/Rel activation

Abstract

In the present study, we demonstrate the inhibitory effect of 2-acetylaminofluorene (AAF) on interleukin-1beta (IL-1beta) gene expression in lipopolysaccharide (LPS)-stimulated macrophages. Acetylaminofluorene inhibited IL-1 production in LPS-stimulated splenic macrophages and RAW 264.7 cells. Additionally, AAF also suppressed LPS-induced mRNA expression of IL-1beta in macrophages. To further characterize the molecular mechanism responsible for AAF-mediated suppression of IL-1beta, we investigated the effect of AAF on LPS-mediated activation of transcription factors, such as NF-kappaB, AP-1, CRE and NF-IL6, which are to be important for LPS-induced gene expression of IL-1beta. Treatment of AAF caused a dose-related inhibition of LPS-induced NF-kappaB/Rel transcriptional activation, while the transcriptional activation of AP-1, CRE and NF-IL6 was not affected by AAF. Furthermore, LPS-induced NF-kappaB/Rel DNA binding was also suppressed by AAF treatment. These results suggest that AAF inhibits IL-1beta gene expression by blocking NF-kappaB/Rel activation. (C) 2004 Elsevier Ireland Ltd. All rights reserved.