Search for the target genes involved in the suppression of antibody production by TCDD in C57BL/6 mice.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses antibody production through activation of a transcription factor, the aryl hydrocarbon receptor (AhR). To explore the genes that are involved in the suppression of antibody production by TCDD, we investigated TCDD-induced changes in gene expression in the CD4 T cells and B cells of C57BL/6 mice immunized with ovalbumin (OVA) plus alum as an adjuvant. Changes in gene expression were analyzed with Affymetrix oligonucleotide microarrays. The results showed that OVA-immunization alone up-regulated expression levels of many genes in the CD4 T cells as early as 3 h after immunization, with 55 up-regulated and 5 down-regulated. At 24 h, 42 genes were found to be up-regulated and 30 down-regulated. Fewer genes were affected in the B cells than in the CD4 T cells. In contrast to the up-regulation of genes induced by immunization in the CD4 T cells, administration of TCDD to mice 3 h prior to the immunization mainly caused down-regulation of genes in the CD4 T cells when compared with immunization alone, with 1 being up-regulated and 4 down-regulated at 3 h after immunization and 3 up-regulated and 34 down-regulated at 24 h. In particular, at 3 and 24 h, TCDD suppressed expression of three and seven genes, respectively, that were up-regulated by immunization. Another characteristic of the TCDD-induced changes in gene expression was the suppression of many genes encoding proteins that are involved in GTP-binding protein-linked signaling in CD4 T cells. These results suggest that the inhibition of immunization-induced gene expression and modulation of G-protein-linked signaling in CD4 T cells are responsible for the TCDD-induced suppression of antibody production.
Nagai
Haruko
H
Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.
Takei
Teiji
T
Tohyama
Chiharu
C
Kubo
Masato
M
Abe
Ryo
R
Nohara
Keiko
K
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010047:Ovalbumin / Q000276:immunology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D000072317:Polychlorinated Dibenzodioxins; D010047:Ovalbumin