In the present study, we demonstrate the inhibitory effect of 2-acetylaminofluorene (AAF) on interleukin-1β (IL-1β) 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-1β in macrophages. To further characterize the molecular mechanism responsible for AAF-mediated suppression of IL-1β, we investigated the effect of AAF on LPS-mediated activation of transcription factors, such as NF-κB, AP-1, CRE and NF-IL6, which are known to be important for LPS-induced gene expression of IL-1β. Treatment of AAF caused a dose-related inhibition of LPS-induced NF-κB/Rel transcriptional activation, while the transcriptional activation of AP-1, CRE and NF-IL6 was not affected by AAF. Furthermore, LPS-induced NF-κB/Rel DNA binding was also suppressed by AAF treatment. These results suggest that AAF inhibits IL-1β gene expression by blocking NF-κB/Rel activation.
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