Transcriptional regulation of intracellular IL-1 receptor antagonist gene by IL-1 alpha in primary mouse keratinocytes

The Journal of Immunology : Official Journal of the American Association of Immunologists
Eunhye La, S M Fischer

Abstract

The inflammatory cytokine IL-1alpha mediates inflammatory reactions in skin and up-regulates the expression of other proinflammatory genes. We previously found that IL-1alpha also increases steady state mRNA levels for intracellular IL-1 receptor antagonist (icIL-1Ra) in primary mouse keratinocytes; however, the mechanism for this was unknown. Here we show that increased expression in primary keratinocytes is due to increased rates of transcription. To study the transcriptional regulation of icIL-1Ra expression induced by IL-1alpha, we functionally characterized 4.5 kb of the 5'-flanking region of the human icIL-1Ra gene. Deletion analysis showed that regulatory elements were contained in the -598- and -288-bp region upstream of the transcription start site. Then we investigated cis- and trans-acting factors required for icIL-1Ra expression and found that a NF-IL-6 site and a NF-kappaB site in the icIL-1Ra promoter were responsible for IL-1alpha-induced icIL-1Ra expression. Moreover, gel shift assays and cotransfection experiments showed that CCAAT/enhancer-binding proteins alpha, beta, and p65 bind to the NF-IL-6 site and NF-kappaB site, respectively, and functionally trans-activate the icIL-1Ra promoter. Finally, mutational a...Continue Reading

References

May 1, 1974·Experimental Cell Research·S H Yuspa, C C Harris
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·T MatsusakaS Akira
Sep 1, 1993·The Biochemical Journal·P N MoynaghL A O'Neill
Mar 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·T NakajimaS Akira
Feb 1, 1996·Biochemical Society Transactions·L A O'Neill
Oct 3, 1996·Nature·Z CaoD V Goeddel
Mar 24, 1998·Immunology Today·M J May, S Ghosh
Nov 7, 1998·The Journal of Biological Chemistry·G J DarlingtonO A MacDougald

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Citations

Jun 26, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tiehui WangChristopher J Secombes
May 18, 2004·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Karen H RedlitzFabio Cominelli
May 1, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stephanie J MelchorSarah E Ewald
Apr 24, 2010·Allergology International : Official Journal of the Japanese Society of Allergology·Aya Nambu, Susumu Nakae
Nov 20, 2009·The Biochemical Journal·Joanne DarraghJ Simon C Arthur
May 20, 2006·Photochemistry and Photobiology·David W C HuntOliver B Utting
Nov 4, 2020·International Journal of Molecular Sciences·Maxence CornutThomas Henry

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