Regulation of expression of human IL-1 alpha and IL-1 beta genes.
IL-1 gene expression was investigated in human blood mononuclear cells. IL-1 alpha and IL-1 beta mRNA were induced with LPS or TNF. Kinetic measurements on Northern blots revealed that these stimuli elicited qualitatively similar changes in IL-1 mRNA levels, and that expression of IL-1 mRNA was tran...
Main Authors: | , , , , |
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格式: | Journal article |
语言: | English |
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1989
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_version_ | 1826279940649123840 |
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author | Turner, M Chantry, D Buchan, G Barrett, K Feldmann, M |
author_facet | Turner, M Chantry, D Buchan, G Barrett, K Feldmann, M |
author_sort | Turner, M |
collection | OXFORD |
description | IL-1 gene expression was investigated in human blood mononuclear cells. IL-1 alpha and IL-1 beta mRNA were induced with LPS or TNF. Kinetic measurements on Northern blots revealed that these stimuli elicited qualitatively similar changes in IL-1 mRNA levels, and that expression of IL-1 mRNA was transient. IL-1 beta mRNA was the predominant mRNA species and remained elevated for somewhat longer than IL-1 alpha mRNA. TNF and IFN-gamma synergized to induce both species of IL-1 mRNA and IL-1 bioactivity. Transcriptional control, as measured by nuclear run on assays, partly determines the greater levels of IL-1 beta mRNA because the rate of IL-1 beta transcription was greater than that of IL-1 alpha. Cycloheximide (CHX) was able to induce IL-1 mRNA but did not induce transcription of either IL-1 gene. When added to cultures pretreated with TNF or LPS, CHX superinduced IL-1 mRNA, but IL-1 transcription was not increased. If added simultaneously CHX blocked TNF-induced IL-1 gene transcription, suggesting that TNF may induce factors required for IL-1 gene transcription. CHX increased the stability of both IL-1 alpha and IL-1 beta mRNA, demonstrating the existence of a post-transcriptional form of control. In half-life experiments IL-1 beta mRNA was more stable than IL-1 alpha mRNA, indicating that post-transcriptional control also contributes to the greater steady state levels of IL-1 beta. Taken together, the available evidence suggests IL-1 alpha and IL-1 beta mRNA are regulated differentially at both the transcriptional and post-transcriptional level. |
first_indexed | 2024-03-07T00:06:19Z |
format | Journal article |
id | oxford-uuid:77a8dc11-6da3-4875-8c9d-a4e1c90387a4 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T00:06:19Z |
publishDate | 1989 |
record_format | dspace |
spelling | oxford-uuid:77a8dc11-6da3-4875-8c9d-a4e1c90387a42022-03-26T20:25:32ZRegulation of expression of human IL-1 alpha and IL-1 beta genes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:77a8dc11-6da3-4875-8c9d-a4e1c90387a4EnglishSymplectic Elements at Oxford1989Turner, MChantry, DBuchan, GBarrett, KFeldmann, MIL-1 gene expression was investigated in human blood mononuclear cells. IL-1 alpha and IL-1 beta mRNA were induced with LPS or TNF. Kinetic measurements on Northern blots revealed that these stimuli elicited qualitatively similar changes in IL-1 mRNA levels, and that expression of IL-1 mRNA was transient. IL-1 beta mRNA was the predominant mRNA species and remained elevated for somewhat longer than IL-1 alpha mRNA. TNF and IFN-gamma synergized to induce both species of IL-1 mRNA and IL-1 bioactivity. Transcriptional control, as measured by nuclear run on assays, partly determines the greater levels of IL-1 beta mRNA because the rate of IL-1 beta transcription was greater than that of IL-1 alpha. Cycloheximide (CHX) was able to induce IL-1 mRNA but did not induce transcription of either IL-1 gene. When added to cultures pretreated with TNF or LPS, CHX superinduced IL-1 mRNA, but IL-1 transcription was not increased. If added simultaneously CHX blocked TNF-induced IL-1 gene transcription, suggesting that TNF may induce factors required for IL-1 gene transcription. CHX increased the stability of both IL-1 alpha and IL-1 beta mRNA, demonstrating the existence of a post-transcriptional form of control. In half-life experiments IL-1 beta mRNA was more stable than IL-1 alpha mRNA, indicating that post-transcriptional control also contributes to the greater steady state levels of IL-1 beta. Taken together, the available evidence suggests IL-1 alpha and IL-1 beta mRNA are regulated differentially at both the transcriptional and post-transcriptional level. |
spellingShingle | Turner, M Chantry, D Buchan, G Barrett, K Feldmann, M Regulation of expression of human IL-1 alpha and IL-1 beta genes. |
title | Regulation of expression of human IL-1 alpha and IL-1 beta genes. |
title_full | Regulation of expression of human IL-1 alpha and IL-1 beta genes. |
title_fullStr | Regulation of expression of human IL-1 alpha and IL-1 beta genes. |
title_full_unstemmed | Regulation of expression of human IL-1 alpha and IL-1 beta genes. |
title_short | Regulation of expression of human IL-1 alpha and IL-1 beta genes. |
title_sort | regulation of expression of human il 1 alpha and il 1 beta genes |
work_keys_str_mv | AT turnerm regulationofexpressionofhumanil1alphaandil1betagenes AT chantryd regulationofexpressionofhumanil1alphaandil1betagenes AT buchang regulationofexpressionofhumanil1alphaandil1betagenes AT barrettk regulationofexpressionofhumanil1alphaandil1betagenes AT feldmannm regulationofexpressionofhumanil1alphaandil1betagenes |