Dioxin stimulates synthesis and secretion of IgE-dependent histamine-releasing factor.

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.

[1]  Y. Fujii‐Kuriyama,et al.  Dioxin induces a novel nuclear factor, DIF‐3, that is implicated in spermatogenesis , 2001, FEBS letters.

[2]  T. Shapiro,et al.  Immune mimicry in malaria: Plasmodium falciparum secretes a functional histamine-releasing factor homolog in vitro and in vivo , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[3]  N. J. Baxter,et al.  Structure of TCTP reveals unexpected relationship with guanine nucleotide-free chaperones , 2001, Nature Structural Biology.

[4]  Y. Fujii‐Kuriyama,et al.  Dioxin suppresses the checkpoint protein, MAD2, by an aryl hydrocarbon receptor-independent pathway. , 2001, Cancer research.

[5]  K. Tanaka,et al.  Characterization of two plastid sigma factors, SigA1 and SigA2, that mainly function in matured chloroplasts in Nicotiana tabacum. , 2000, Gene.

[6]  D. MacGlashan,et al.  Human recombinant histamine-releasing factor activates human eosinophils and the eosinophilic cell line, AML14-3D10. , 2000, Blood.

[7]  Kyunglim Lee,et al.  Expression of translationally controlled tumor protein mRNA in human colon cancer. , 2000, Cancer letters.

[8]  X. Dumont,et al.  Identification and transcription control of fission yeast genes repressed by an ammonium starvation growth arrest , 2000, Yeast.

[9]  Y. Gachet,et al.  The growth-related, translationally controlled protein P23 has properties of a tubulin binding protein and associates transiently with microtubules during the cell cycle. , 1999, Journal of cell science.

[10]  J. Peters,et al.  Amelioration of TCDD-induced teratogenesis in aryl hydrocarbon receptor (AhR)-null mice. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[11]  K. Rokutan,et al.  Macrophage colony-stimulating factor stimulates synthesis and secretion of a mouse homolog of a human IgE-dependent histamine-releasing factor by macrophages in vitro and in vivo. , 1998, Journal of immunology.

[12]  H. Zinszner,et al.  Identification of novel stress‐induced genes downstream of chop , 1998, The EMBO journal.

[13]  J M Rice,et al.  An IARC evaluation of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans as risk factors in human carcinogenesis. , 1998, Environmental health perspectives.

[14]  Y. Fujii‐Kuriyama,et al.  Ah receptor, a novel ligand-activated transcription factor. , 1997, Journal of biochemistry.

[15]  Kenji Nakamura,et al.  Loss of teratogenic response to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) in mice lacking the Ah (dioxin) receptor , 1997, Genes to cells : devoted to molecular & cellular mechanisms.

[16]  J. Schroeder,et al.  Recombinant histamine-releasing factor enhances IgE-dependent IL-4 and IL-13 secretion by human basophils. , 1997, Journal of immunology.

[17]  J M Ward,et al.  Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity. , 1996, Toxicology and applied pharmacology.

[18]  T. Rafnar,et al.  Molecular identification of an IgE-dependent histamine-releasing factor. , 1995, Science.

[19]  T. Pineau,et al.  Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor , 1995, Science.

[20]  Alexandra L. Joyner,et al.  Gene targeting: a practical approach. , 1993 .

[21]  D W Nebert,et al.  The Ah locus: genetic differences in toxicity, cancer, mutation, and birth defects. , 1989, Critical reviews in toxicology.

[22]  C. Schiller,et al.  Dose-related effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in C57BL6J and DBA2J mice , 1985 .