Duration of α1-antichymotrypsin gene activation by interleukin-1 is determined by efficiency of inhibitor of nuclear factor κBα resynthesis in primary human astrocytes

Daniel L. Kiss, Weili Xu, Sunita Gopalan, Katarzyna Buzanowska, Katarzyna M. Wilczynska, Russell E. Rydel, Tomasz Kordula

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Expression of α1antichymotrypsin (ACT) is significantly activated by interleukin-1 (IL-1) in human astrocytes; however, it is barely affected by IL-1 in hepatocytes. This tissue-specific regulation depends upon an enhancer that contains both nuclear factor κB (NF-κB) and activating protein 1 (AP-1) elements, and is also observed for an NF-κB reporter but not for an AP-1 reporter. We found efficient activation of NF-κB binding in both cell types; however, this binding was persistent in glial cells and only transient in hepatocytes. IL-1-activated NF-κB complexes consisted of p65 and p50, with p65 transiently phosphorylated on serine 536 in glial cells whereas more persistently in hepatic cells. Overexpression of p65 or constitutively active IKKβ (inhibitor of NF-κB kinase β) resulted in an efficient activation of the ACT reporter in hepatic cells, indicating that a specific mechanism exists in these cells terminating IL-1 signaling. IL-1 effectively induced the degradation of inhibitor of NF-κBα (IkBα) and IkBε in both cell types but IkBβ was not affected. However, IkBα was resynthesized much more rapidly in hepatic cells in comparison to glial cells. In addition, the initial levels of IkBα were much lower in glial cells. We propose that the tissue-specific regulation of the ACT gene expression by IL-1 is determined by different efficiencies of IkBα resynthesis in glial and hepatic cells.

Original languageEnglish (US)
Pages (from-to)730-738
Number of pages9
JournalJournal of Neurochemistry
Volume92
Issue number4
DOIs
StatePublished - Feb 2005

Keywords

  • Astrocytes
  • Expression
  • Interleukin-1
  • Nuclear factor κB
  • α-antichymotrypsin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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