Aryl hydrocarbon receptor/dioxin receptor in human monocytes and macrophages.
Aryl hydrocarbon receptor (AhR) belongs to the bHLH/PAS transcription factor family and is activated by various polycyclic or halogenated aromatic hydrocarbons, e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (3MC). In the present study, we showed that in U937 cells and human macrophages AhR, with its partner cofactor Arnt, is expressed and CYP1A1 mRNA expression is induced in the presence of AhR ligand 3MC. Moreover, we showed that AhR, associating with Arnt, binds to target DNA sequences and activates transcription. Since part of AhR is activated into DNA binding species in the absence of exogenous ligand and competitive AhR antagonist alpha-naphthoflavone inhibits this activation process with reducing CYP1A1 mRNA expression levels, the presence of endogenous ligand is indicated.
Komura
K
K
Second Department of Internal Medicine, Asahikawa Medical College, Midorigaoka Higashi, Japan.
Hayashi
S
S
Makino
I
I
Poellinger
L
L
Tanaka
H
H
D001571:Benzoflavones / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D006801:Humans; D015151:Immunoblotting; D008024:Ligands; D008156:Luciferases / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008748:Methylcholanthrene / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D020298:U937 Cells
D001571:Benzoflavones; D008024:Ligands; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D008748:Methylcholanthrene; C011512:alpha-naphthoflavone; D004247:DNA; D008156:Luciferases; D019363:Cytochrome P-450 CYP1A1