Induction and activation of the aryl hydrocarbon receptor by IL-4 in B cells

• Published in: International immunology Vol. 17; no. 6; pp. 797 - 805
• Main Authors: Tanaka, Go, Kanaji, Sachiko, Hirano, Ayumi, Arima, Kazuhiko, Shinagawa, Akira, Goda, Chiho, Yasunaga, Shin'ichiro, Ikizawa, Koichi, Yanagihara, Yukiyoshi, Kubo, Masato, Kuriyama-Fujii, Yoshiaki, Sugita, Yuji, Inokuchi, Akira, Izuhara, Kenji
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.06.2005; Oxford Publishing Limited (England)
• Subjects: 8-tetra-chlorodibenzo-p-dioxin; AhR aryl hydrocarbon receptor; Animals; Arnt aryl hydrocarbon receptor nuclear translocator; Burkitt Lymphoma - enzymology; Burkitt Lymphoma - genetics; Burkitt Lymphoma - metabolism; Cell Line; Cell Line, Tumor; Cell Nucleus - drug effects; Cell Nucleus - metabolism; CYP1A1; CYP1A1 cytochrome P4501A1; Cytochrome P-450 CYP1A1 - metabolism; dioxin; Environmental Pollutants - toxicity; gene regulation; HA-STAT6DN hemagglutinin-tagged truncated form of STAT6; HDAC1 histone deacetylase class 1; Humans; Interleukin-13 - pharmacology; Interleukin-4 - pharmacology; Lymphoma, B-Cell - enzymology; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; microarray; Plasmids; Polychlorinated Dibenzodioxins - toxicity; Receptors, Aryl Hydrocarbon - biosynthesis; Receptors, Aryl Hydrocarbon - immunology; RT reverse transcription; TCDD 2; Transfection; xenobiotics
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxh260

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.