Rottlerin, a PKC isozyme-selective inhibitor, affects signaling events and cytokine production in human monocytes

Kontny, E., Kurowska, M. , Szczepańska, K. and Maśliński, W. (2000) Rottlerin, a PKC isozyme-selective inhibitor, affects signaling events and cytokine production in human monocytes. Journal of Leukocyte Biology, 67(2), pp. 249-258.

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Publisher's URL: http://www.jleukbio.org/content/67/2/249.abstract

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 PKCalpha and delta 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 microM) concentration it blocks translocation of PKCdelta, diminishes DNA binding activity of AP-1 transcription factor, and attenuates cytokine production [tumor necrosis factor alpha (TNF-alpha) > interleukin-1beta (IL-1beta)]. (2) At high (50 microM) concentration it prevents translocation of PKCalpha, and subsequently inhibits ERK1/ERK2 phosphorylation, DNA binding activities of AP-1 and nuclear factor-KB transcription factors, and the production of both tested cytokines. Thus, we propose that cytosol-to-membrane translocation of PKCalpha and PKdelta isoenzymes may represent early steps in the signaling cascades that lead to TNF-alpha and IL-1beta production in human monocytes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kurowska-Stolarska, Dr Mariola
Authors: Kontny, E., Kurowska, M., Szczepańska, K., and Maśliński, W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Leukocyte Biology
Publisher:Society for Leukocyte Biology
ISSN:0741-5400
ISSN (Online):1938-3673

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