Regulation of HLA-DR gene by IFN-gamma. Transcriptional and post-transcriptional control.
IFN-gamma increases the synthesis and level of mRNA of the HLA class I and II genes, in human cells such as melanomas which normally express both classes of molecules. It also induces the surface expression and mRNA synthesis of HLA-DR genes on cells which normally do not express HLA class II genes such as skin fibroblasts. We have investigated the mechanism by which IFN-gamma increases mRNA levels for class II MHC antigens in human cells. For this purpose, we have studied the effect of IFN-gamma on HLA-DR-alpha transcription rate in two different human cell types: VAL melanoma and JDA2 skin fibroblasts. HLA-DR-alpha mRNA is spontaneously produced in VAL cells and its level is enhanced upon IFN-gamma treatment. We demonstrate here that IFN-gamma increases the transcription of HLA-DR-alpha gene in this cell line. However, the discrepancy observed between HLA-DR-alpha mRNA and transcriptional rates led us to postulate that IFN-gamma also regulates the HLA-DR-alpha gene post-transcriptionally. In the course of these experiments, we found also that human skin fibroblasts, which do not contain detectable amounts of HLA-DR-alpha mRNA, spontaneously transcribe the HLA-DR-alpha gene.
D002460:Cell Line; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006681:HLA-D Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000032:analysis / Q000235:genetics / Q000276:immunology; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D012867:Skin / Q000166:cytology; D014158:Transcription, Genetic / Q000187:drug effects*
D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D007371:Interferon-gamma