International Immunology Advance Access originally published online on May 17, 2005
International Immunology 2005 17(6):797-805; doi:10.1093/intimm/dxh260
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Induction and activation of the aryl hydrocarbon receptor by IL-4 in B cells
1 Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, 5-1-1 Nabeshima, Saga, 849-8501, Japan
2 Genox Research Inc., 5-12-8, Koishikawa, Tokyo, 112-8088, Japan
3 Hanno Research Center, Taiho Pharmaceutical Co., Ltd., 1-27, Misugidai, Hanno, 357-8527, Japan
4 Clinical Research Center, National Sagamihara Hospital, 18-1, Sakuradai, Sagamihara, 228-8522, Japan
5 RIKEN Research Center for Allergy and Immunology, (RCAI), RIKEN Yokohama Institute, Yokohama, 1-7-22, Suehiro-cho, Yokohama, 230-0045, Japan
6 Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1, Tenoudai, Tsukuba, 305-8577, Japan
7 Department of Otolaryngology-Head and Neck Surgery and 8 Division of Medical Research, Center for Comprehensive Community Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga, 849-8501, Japan
Correspondence to: K. Izuhara; E-mail: kizuhara{at}med.saga-u.ac.jp
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.
Keywords: CYP1A1, dioxin, gene regulation, microarray, xenobiotics
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