Protein kinase C-alpha and -beta play antagonistic roles in the differentiation process of THP-1 cells

Cell Signal. 2000 May;12(5):297-302. doi: 10.1016/s0898-6568(00)00069-3.

Abstract

The roles of protein kinase C (PKC) isoenzymes in the differentiation process of THP-1 cells are investigated. Inhibition of PKC by RO 31-8220 reduces the phagocytosis of latex particles and the release of superoxide, prostaglandin E(2) (PGE(2)), and tumour necrosis factor (TNF)-alpha. The proliferation of THP-1 cells is slightly enhanced by RO 31-8220. Stable transfection of THP-1 cells with asPKC-alpha, and incubation of THP-1 cells with antisense (as) PKC-alpha oligodeoxynucleotides reduces PKC-alpha levels and PKC activity. asPKC-alpha-transfected THP-1 cells show a decreased phagocytosis and a decreased release of superoxide, PGE(2) and TNF-alpha. The proliferation of asPKC-alpha-transfected THP-1 cells is enhanced. Stable transfection of THP-1 cells with asPKC-beta, and incubation of THP-1 cells with asPKC-beta oligodeoxynucleotides, reduces PKC-beta levels and PKC activity. asPKC-beta-transfected THP-1 cells show a decreased phagocytosis, a decreased TNF-alpha release, and a decreased proliferation. However, no difference is measured in the release of superoxide and PGE(2). These results suggest that: (1) PKC-alpha but not PKC-beta is involved in the release of superoxide and PGE(2); (2) TNF-alpha release and the phagocytosis of latex particles are mediated by PKC-alpha, PKC-beta, and other PKC isoenzymes; and (3) PKC-alpha and PKC-beta play antagonistic roles in the differentiation process of THP-1 cells. PKC-alpha promotes the differentiation process of THP-1 cells, PKC-beta retards the differentiation of THP-1 cells into macrophage-like cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Indoles / pharmacology
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Leukemia, Monocytic, Acute
  • Monocytes / cytology*
  • Monocytes / enzymology*
  • Oligonucleotides, Antisense / pharmacology
  • Plasmids
  • Prostaglandins / physiology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Kinase C beta
  • Protein Kinase C-alpha
  • Signal Transduction / immunology*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Enzyme Inhibitors
  • Indoles
  • Isoenzymes
  • Oligonucleotides, Antisense
  • Prostaglandins
  • PRKCA protein, human
  • Protein Kinase C
  • Protein Kinase C beta
  • Protein Kinase C-alpha
  • Ro 31-8220