In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 67, No. 2 ( 2000-02-01), p. 249-258
Abstract:
The implication of select protein kinase C (PKC) isoenzymes in cytokine production by human monocytes was investigated using an isozyme-selective inhibitor of PKC, rottlerin. We found that lipopolysaccharide (LPS) triggers cytosol-to-membrane translocation of PKCα and δ isoenzymes, whereas phorbol ester (PMA) induces translocation of several PKC isoforms. Moreover, we show that in LPS- and PMA-stimulated monocytes rottlerin affects several cellular responses. (1) At low (15 μM) concentration it blocks translocation of PKCδ, diminishes DNA binding activity of AP-1 transcription factor, and attenuates cytokine production [tumor necrosis factor α (TNF-α) & gt; interleukin-1β (IL-1β)]. (2) At high (50 μM) concentration it prevents translocation of PKCα, and subsequently inhibits ERK1/ERK2 phosphorylation, DNA binding activities of AP-1 and nuclear factor-κB transcription factors, and the production of both tested cytokines. Thus, we propose that cytosol-to-membrane translocation of PKCα and PKδ isoenzymes may represent early steps in the signaling cascades that lead to TNF-α and IL-1β production in human monocytes. J. Leukoc. Biol. 67: 249–258; 2000.
Type of Medium:
Online Resource
ISSN:
0741-5400
,
1938-3673
DOI:
10.1002/jlb.67.2.249
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2000
detail.hit.zdb_id:
2026833-6
SSG:
12
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