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Divergent effect of proteasome inhibition on interleukin‐1β and tumor necrosis factor α signaling in human astroglial cells
Author(s) -
Choi Kyungsun,
Lee Jungsul,
Choi Chulhee
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.08.065
Subject(s) - proteasome , tumor necrosis factor alpha , microbiology and biotechnology , kinase , signal transduction , biology , interleukin , chemokine , c jun , cancer research , chemistry , cytokine , immunology , inflammation , biochemistry , transcription factor , gene
Impaired functioning of the proteasome pathway is one of the molecular mechanism underlying neurodegenerative changes in Alzheimer's disease. In this study, we report that dysfunction of the proteasome pathway in astroglial cells leads to decreased survival and dysregulation of chemokines by differential regulation of the nuclear factor kappa B and c‐jun N‐terminal kinase (JNK) pathways. We further demonstrated that proteasome inhibition augmented interleukin‐1 β‐ and tumor necrosis factor‐α‐induced activation of the IκBα kinase and MKK4/JNK/c‐Jun pathway along with TAK1 activation. These results suggest that impaired function of the proteasome pathway may potentiate the immuno‐pathologic role of secondarily activated astrocytes in the brain.