Identification of AhR-regulated genes involved in PAH-induced immunotoxicity using a highly-sensitive DNA chip, 3D-Gene Human Immunity and Metabolic Syndrome 9k.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants with various toxic effects including immune suppression. However, the molecular mechanism of their toxicity has not been fully clarified. The purpose of this study was to identify novel aryl hydrocarbon receptor (AhR)-regulated genes involved in PAH-induced immunotoxicity using a highly-sensitive DNA chip, 3D-Gene(TM) Human Immunity & Metabolic Syndrome 9k. Leucine-rich repeat-containing protein 25, glucosaminyl (N-acetyl) transferase 3 (GCNT3), thyroxine-binding globulin, aldehyde dehydrogenase 8A1, diacylglycerol O-acyltransferase homolog 2 (DGAT2), haptoglobin, neuron navigator 2 isoform 1, hemopexin and bile acid receptor were found to be up- or down-regulated by PAHs via AhR. Among these genes, GCTN3 and DGAT2 were responsible for immune responses. Therefore, disruption of the expression of these genes via AhR may be one of the causes of the immunotoxicity of PAHs.
Iwano
Shunsuke
S
Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries Inc., Kamakura, Kanagawa, Japan.
Ichikawa
Makiko
M
Takizawa
Satoko
S
Hashimoto
Hisashi
H
Miyamoto
Yohei
Y
D001564:Benzo(a)pyrene / Q000633:toxicity; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007109:Immunity / Q000235:genetics*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D024821:Metabolic Syndrome / Q000235:genetics*; D009153:Mutagens / Q000633:toxicity; D020411:Oligonucleotide Array Sequence Analysis; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D019324:beta-Naphthoflavone / Q000633:toxicity
D007166:Immunosuppressive Agents; D009153:Mutagens; D011084:Polycyclic Aromatic Hydrocarbons; D034741:RNA, Small Interfering; D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene; D019324:beta-Naphthoflavone; D012313:RNA