Selective activation of specific PKC isoforms dictating the fate of CD14+ monocytes towards differentiation or apoptosis

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

In this study, phorbol-12-myristate-13-acetate (PMA) at low concentrations (+ 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-+ 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.

Original languageEnglish
Pages (from-to)122-131
Number of pages10
JournalJournal of Cellular Physiology
Volume226
Issue number1
DOIs
Publication statusPublished - Jan 2011

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Fingerprint Dive into the research topics of 'Selective activation of specific PKC isoforms dictating the fate of CD14<sup>+</sup> monocytes towards differentiation or apoptosis'. Together they form a unique fingerprint.

Cite this