TY - JOUR
T1 - Duration of α1-antichymotrypsin gene activation by interleukin-1 is determined by efficiency of inhibitor of nuclear factor κBα resynthesis in primary human astrocytes
AU - Kiss, Daniel L.
AU - Xu, Weili
AU - Gopalan, Sunita
AU - Buzanowska, Katarzyna
AU - Wilczynska, Katarzyna M.
AU - Rydel, Russell E.
AU - Kordula, Tomasz
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/2
Y1 - 2005/2
N2 - 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.
AB - 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.
KW - Astrocytes
KW - Expression
KW - Interleukin-1
KW - Nuclear factor κB
KW - α-antichymotrypsin
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U2 - 10.1111/j.1471-4159.2004.02900.x
DO - 10.1111/j.1471-4159.2004.02900.x
M3 - Article
C2 - 15686474
AN - SCOPUS:13644268433
SN - 0022-3042
VL - 92
SP - 730
EP - 738
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 4
ER -