Involvement of an inducible factor in interferon-γ-mediated accumulation of HLA gene transcripts Journal Article
| Authors: | Gupta, S. L.; Sharma, G.; Caplen, H. S.; Pyati, P.; Burnett, P. M. |
| Article Title: | Involvement of an inducible factor in interferon-γ-mediated accumulation of HLA gene transcripts |
| Abstract: | Earlier studies with a cDNA clone (C5-4) complementary to an interferon (IFN)-γ-inducible mRNA showed that in human fibroblasts (FS-4), IFN-γ induced the transcription of the cognate gene, but it required new protein synthesis (Caplen and Gupta, J. Biol. Chem. 263, 332-339, 1988). To determine whether such a strategy is used for the regulation of other cellular genes by IFN-γ, the regulation of the HLA class I and class II genes and another cellular gene for which a cDNA clone was isolated (C13) was studied. The results indicate that: (i) HLA-B (class I) and C13 gene expression was transcriptionally activated by IFN-γ and IFN-α2, and it did not require new protein synthesis, (ii) In contrast, the transcription of the HLA-DRα was activated by IFN-γ (and not by IFN-α2), but the accumulation of −DRα gene transcripts was strongly inhibited by cycloheximide or anisomycin, which indicated that there was a requirement for some newly synthesized protein factor(s) in this process, apparently at a step subsequent to transcriptional activation. We obtained evidence indicating that the putative protein factor(s) required is actually induced by IFN-γ. (iii) IFN-γ-induced transcription of the HLA-B gene was not inhibited by anisomycin or cycloheximide, but the accumulation of HLA-B transcripts plateaued sooner. This latter effect was not due to any toxicity of these inhibitors because it was observed if cycloheximide was added together with IFN-γ, but not if it was added a few hours later. Furthermore, if cycloheximide was added 24 h after IFN-γ, it actually caused a superinduction of HLA-B transcripts. The results suggest that some newly synthesized protein factor(s) may be required also for maximal accumulation of HLA-B gene transcripts following treatment with IFN-γ. The results indicate a dual regulation of HLA class I and class II genes by IFN-γ, and involvement of multiple mechanisms in the regulation of cellular gene expression by IFN-γ. © 1989, Mary Ann Liebert, Inc. All rights reserved. |
| Keywords: | gene expression; genetic transcription; gamma interferon; genetic engineering; major histocompatibility complex; rna processing, post-transcriptional; interferon type i; alpha2 interferon; cycloheximide; interferon type ii; genes, mhc class i; human; priority journal; article; support, u.s. gov't, p.h.s.; hla class 1 gene; hla class 2 gene |
| Journal Title: | Journal of Interferon Research |
| Volume: | 9 |
| Issue: | 5 |
| ISSN: | 0197-8357 |
| Publisher: | Mary Ann Liebert, Inc |
| Date Published: | 1989-10-01 |
| Start Page: | 531 |
| End Page: | 542 |
| Language: | English |
| DOI: | 10.1089/jir.1989.9.531 |
| PUBMED: | 2507660 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 14 April 2020 -- Source: Scopus |
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