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Interleukin‐1β and Tumor Necrosis Factor‐α Induce Expression of α 1 ‐Antichymotrypsin in Human Astrocytoma Cells by Activation of Nuclear Factor‐κB
Author(s) -
Lieb Klaus,
Fiebich Bernd L.,
Schaller Helen,
Berger Mathias,
Bauer Joachim
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67052039.x
Subject(s) - tumor necrosis factor alpha , astrocytoma , tumor necrosis factor α , cancer research , biology , pathology , glioma , immunology , medicine
The protease inhibitor α 1 ‐antichymotrypsin (ACT) has been suggested to be involved in the etiology of Alzheimer's disease (AD). Increased levels of ACT have been found in serum and brains of AD patients, and ACT has been proposed to regulate β‐amyloid fibril formation in vitro. To gain insight into the regulation of ACT in the brain, we investigated the signal transduction pathways involved in ACT gene expression and protein synthesis in the human astrocytoma cell line U373. This cell line has previously been shown to respond with strong ACT synthesis on stimulation with interleukin‐1β (IL‐1β) or tumor necrosis factor‐α (TNFα). Here, we describe that both IL‐1β and TNFα activate the transcription factor nuclear factor‐κB (NF‐κB) via production of reactive oxygen intermediates resulting in ACT expression. In addition, we show that neither protein kinase C nor protein kinase A is involved in IL‐1β‐ or TNFα‐induced ACT expression. These results suggest that activation of NF‐κB may be one possible cause of increased ACT levels in AD and provide a basis for the development of drugs used for the modulation of inflammatory processes occurring in AD.