Selective activation of specific PKC isoforms dictating the fate of CD14+ monocytes towards differentiation or apoptosis |
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| Authors: | Yuan‐Feng Lin Sy‐Jye Leu Huei‐Mei Huang Yu‐Hui Tsai |
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| Institution: | 1. School of Pharmacy, Taipei Medical University (TMU), Taipei, Taiwan, ROC;2. Graduate Institute of Medical Sciences, College of Medicine, TMU, Taipei, Taiwan, ROC;3. Department of Microbiology and Immunology, College of Medicine, TMU, Taipei, Taiwan, ROC;4. Center for Reproductive Medicine, and Center for Nano‐Tissue Engineering and Imaging Research, TMU Hospital (TMUH), Taipei, Taiwan, ROC;5. Department of Physical Medicine and Rehabilitation, TMUH, Taipei, Taiwan, ROC |
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| Abstract: | 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/β1 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, β1, and β2 isoforms was observed in the H‐PMA‐treated CD14+ monocytes, only PKC‐β2 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‐β1 induces the differentiation of CD14+ monocytes into MDMs or dendritic cells (MoDCs), respectively, the results in this study further demonstrate that PKC‐β2 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. |
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