Down-regulation of major histocompatibility complex Q1(b) gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin

We analyzed mouse hepatoma cells using differential display to discover new genes that respond to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We identified a class I major histocompatibility complex (MHC) gene, which we designated as MHC Q1(b), whose expression decreases in the presence of TCDD. TCDD-induced down-regulation of MHC Q1(b) requires both the aromatic hydrocarbon receptor and the aromatic hydrocarbon receptor nuclear translocator, transcription factors that up-regulate other genes in response to TCDD. Down-regulation of MHC Q1(b) by TCDD appears to involve both transcriptional and posttranscriptional regulatory events; the post-transcriptional destabilization of MHC Q1(b) mRNA is probably a secondary response to TCDD. Our findings reveal new mechanistic aspects of gene regulation by TCDD, In addition, our observations suggest a mechanism that might account for some of TCDD's immunotoxic effects.