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Selective activation of specific PKC isoforms dictating the fate of CD14 + monocytes towards differentiation or apoptosis
Author(s) -
Lin YuanFeng,
Leu SyJye,
Huang HueiMei,
Tsai YuHui
Publication year - 2011
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22312
Subject(s) - cd14 , protein kinase c , apoptosis , monocyte , microbiology and biotechnology , phorbol , caspase , chemistry , signal transduction , biology , programmed cell death , flow cytometry , immunology , biochemistry
In this study, phorbol‐12‐myristate‐13‐acetate (PMA) at low concentrations (<10 nM; L‐PMA) induces the differentiation of CD14 + monocytes into monocyte‐derived macrophages (MDMs) while PMA at high concentrations (>100 nM; H‐PMA) causes the apoptosis of these cells. The pre‐treatment with Go6976 (a PKC‐α/β 1 selective inhibitor), not anilinemonoindolylmaleimide [a PKC‐β inhibitor (PKC‐β inh.)], significantly ( P < 0.05) reduces the L‐PMA‐induced generation of MDMs in the cultured CD14 + monocytes. On the other hand, either of the above two PKC inhibitors is capable of suppressing the H‐PMA‐induced apoptosis of CD14 + monocytes. However, only the inclusion of PKC‐β inh., not Go6976, prevents the cells from serum deprivation‐induced cell apoptosis. Although the membrane translocation of conventional PKC‐α, β 1 , and β 2 isoforms was observed in the H‐PMA‐treated CD14 + monocytes, only PKC‐β 2 exhibits a mitochondrial translocation activity among those PKCs responsive to H‐PMA treatment. Moreover, the activation of DEVD‐dependent caspases (DEVDase) was also detected in the H‐PMA‐treated CD14 + monocytes, indicating the involvement of a caspase‐dependent signaling pathway in the H‐PMA‐induced cell apoptosis of CD14 + monocytes. Together with our previous findings that the selective activation of PKC‐α or PKC‐β 1 induces the differentiation of CD14 + monocytes into MDMs or dendritic cells (MoDCs), respectively, the results in this study further demonstrate that PKC‐β 2 activation is responsible for relaying the apoptotic signal to intrinsic mitochondria‐dependent caspase signaling cascades in the CD14 + monocytes. It is likely that the selective activation of specific PKC isoforms provides a new strategy to manipulate the differential cell fate commitment of multipotent CD14 + monocytes towards apoptosis or differentiation into MDMs, MoDCs, and other cell types. J. Cell. Physiol. 226: 122–131, 2010. © 2010 Wiley‐Liss, Inc.