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

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)...

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Published in:Journal of neurochemistry 2005-02, Vol.92 (4), p.730-738
Main Authors: Kiss, Daniel L., Xu, Weili, Gopalan, Sunita, Buzanowska, Katarzyna, Wilczynska, Katarzyna M., Rydel, Russell E., Kordula, Tomasz
Format: Article
Language:English
Subjects:
astrocytes
Biological and medical sciences
expression
Fundamental and applied biological sciences. Psychology
interleukin‐1
Isolated neuron and nerve. Neuroglia
Molecular and cellular biology
Molecular genetics
nuclear factor κB
Transcription. Transcription factor. Splicing. Rna processing
Vertebrates: nervous system and sense organs
α1‐antichymotrypsin
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Summary: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.
ISSN:0022-3042
1471-4159
DOI:10.1111/j.1471-4159.2004.02900.x