title: Dioxin stimulates synthesis and secretion of IgE-dependent histamine-releasing factor.
abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; dioxin) is the most toxic man-made member of the class of environmental pollutants represented by polychlorinated dibenzo-p-dioxins and dibenzofurans. TCDD produces a wide variety of toxic effects. However, the downstream genes targeted by TCDD and their relation to the diversity of dioxin toxicity symptoms are poorly understood. To identify the target genes of TCDD, we used a cDNA representational difference analysis (RDA) to compare the mRNA patterns of mouse embryonic stem (ES) cells that had and had not been exposed to TCDD. Here we show that TCDD stimulated the expression of IgE-dependent histamine-releasing factor (HRF) mRNA via an aryl hydrocarbon receptor (AhR)-dependent pathway. TCDD also induced the synthesis and secretion of HRF. To our knowledge, this is the first example of HRF being a direct transcriptional target of a toxic agent. HRF has previously been shown to induce histamine release in a dose-dependent manner, at least in vitro. Thus, our data suggest that "endocrine-disrupting" agents may have the potential to influence allergic disorders in the human body.
authors.affiliation: Department of Pathology, Tokyo Medical University, Shinjuku-ku, Tokyo, 160-8402, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Oikawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ohbayashi
authors.forename: Junsei
authors.initials: J
authors.lastname: Mimura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fujii-Kuriyama
authors.forename: Shigetada
authors.initials: S
authors.lastname: Teshima
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Rokutan
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Mukai
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kuroda
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000494:pharmacology*; D006636:Histamine Release; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000502:physiology; D015533:Transcriptional Activation; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D014408:Biomarkers, Tumor; D004785:Environmental Pollutants; D008222:Lymphokines; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D000090324:Tumor Protein, Translationally-Controlled 1