title: Induction and activation of the aryl hydrocarbon receptor by IL-4 in B cells.
abstract: It is widely known that IL-4 and IL-13 act on various kinds of cells, including B cells, resulting in enhancement of proliferation, class switching to IgE and expression of several surface proteins. These functions are important for the recognition of the various antigens in B cells and are known to be involved in the pathogenesis of allergic diseases. However, it has not been known whether IL-4/IL-13 is involved in the metabolism of various kinds of xenobiotics including 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), and it remains undetermined whether TCDD, an environmental pollutant, influences IgE production in B cells, exaggerating allergic reactions. We identified IL-4- or IL-13-inducible genes in a human Burkitt lymphoma cell line, DND-39, using microarray technology, in which the AHR gene was included. The AHR gene product, the aryl hydrocarbon receptor (AhR), was induced by IL-4 in both mouse and human B cells in a STAT6-dependent manner. IL-4 alone had the ability to translocate the induced AhR to the nuclei. TCDD, a ligand for AhR, rapidly degraded the induced AhR by the proteasomal pathway, although IL-4-activated AhR sustained its expression. AhR activated by IL-4 caused expression of a xenobiotic-metabolizing gene, CYP1A1, and TCDD synergistically acted on the induction of this gene by IL-4. However, the induction of AhR had no effect on IgE synthesis or CD23 expression. These results indicate that the metabolism of xenobiotics would be a novel biological function of IL-4 and IL-13 in B cells, whereas TCDD is not involved in IgE synthesis in B cells.
authors.affiliation: Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Tanaka
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kanaji
authors.forename: Ayumi
authors.initials: A
authors.lastname: Hirano
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Arima
authors.forename: Akira
authors.initials: A
authors.lastname: Shinagawa
authors.forename: Chiho
authors.initials: C
authors.lastname: Goda
authors.forename: Shin'ichiro
authors.initials: S
authors.lastname: Yasunaga
authors.forename: Koichi
authors.initials: K
authors.lastname: Ikizawa
authors.forename: Yukiyoshi
authors.initials: Y
authors.lastname: Yanagihara
authors.forename: Masato
authors.initials: M
authors.lastname: Kubo
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kuriyama-Fujii
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sugita
authors.forename: Akira
authors.initials: A
authors.lastname: Inokuchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Izuhara
mesh_terms: D000818:Animals; D002051:Burkitt Lymphoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D016393:Lymphoma, B-Cell / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010957:Plasmids; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis* / Q000276:immunology; D014162:Transfection
chemical_list: D004785:Environmental Pollutants; D018793:Interleukin-13; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D015847:Interleukin-4; D019363:Cytochrome P-450 CYP1A1