2-Acetylaminofluorene inhibits interleukin-1beta production in LPS-stimulated macrophages by blocking NF-kappaB/Rel activation.
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 known 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.
Kang
Jong Soon
JS
Biopotency Evaluation Laboratory, Korea Research Institute of Bioscience and Biotechnology, 52 Oun-dong, Yuseong-gu, 305-333 Taejon, South Korea.
Jeon
Young Jin
YJ
Suh
Jaehong
J
Park
Song-Kyu
SK
Yang
Kyu-Hwan
KH
Kim
Hwan Mook
HM
D015073:2-Acetylaminofluorene / Q000494:pharmacology*; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D004789:Enzyme Activation; D005260:Female; D005786:Gene Expression Regulation; D020573:Genes, rel; D007375:Interleukin-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000096:biosynthesis*
D002273:Carcinogens; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D015073:2-Acetylaminofluorene