Aryl hydrocarbon receptor-mediated posttranscriptional regulation of IL-1beta.
TCDD stimulated IL-1beta gene expression in differentiating human keratinocyte cell lines in a time- and dose-dependent manner. Increases in prointerleukin-1beta (pIL-1beta) protein and IL-1beta steady state mRNA levels were observed in both SCC-12F and HaCaT cells following TCDD treatment. When pretreated with alpha-naphthoflavone, an AhR antagonist, TCDD-mediated increases in IL-1beta gene expression were attenuated, demonstrating for the first time that the environmental toxin, TCDD, can stimulate cytokine (IL-1beta) gene expression in an AhR-dependent manner. Nuclear run-on experiments were performed in SCC-12 cells to determine if the AhR-dependent increases in IL-1beta expression were due to transcriptional activation of the IL-1beta gene. Results showed high constitutive levels of IL-1beta transcriptional activity, however, TCDD treatment, which stimulated IL-1beta steady state mRNA levels, failed to potentiate IL-1beta transcription. Taken together, these results demonstrate that AhR-mediated IL-1beta regulation is occurring posttranscriptionally.
Henley
Derek V
DV
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, MO, USA.
Bellone
Clifford J
CJ
Williams
Debbie A
DA
Ruh
Thomas S
TS
Ruh
Mary F
MF
D001571:Benzoflavones / Q000494:pharmacology; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D014162:Transfection
D001571:Benzoflavones; D007375:Interleukin-1; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; C011512:alpha-naphthoflavone; D008156:Luciferases