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

The roles of protein kinase C (PKC) isoenzymes in the differentiation proce ss of THP-1 cells are investigated. Inhibition of PKC by RO 31-8220 reduces the phagocytosis of latex particles and the release of superoxide, prostag landin E-2 (PGE(2)), and tumour necrosis factor (TNF)-alpha. The proliferat ion 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 antisen se (as) PKC-a oligodeoxynucleotides reduces PKC-alpha levels and PKC activi ty. asPKC-alpha-transfected THP-1 cells show a decreased phagocytosis and a decreased release of superoxide, PGE(2) and TNF-alpha. The proliferation o f asPKC-alpha-transfected THP-1 cells is enhanced. Stable transfection of T HP-1 cells with asPKC-beta, and incubation of THP-1 cells with asPKC-beta o ligodeoxynucleotides, reduces PKC-beta levels and PKC activity. asPKC-beta- transfected THP-1 cells show a decreased phagocytosis, a decreased TNF-a re lease, 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 PK C-beta play antagonistic roles in the differentiation process of THP-1 cell s. PKC-alpha, promotes the differentiation process of THP-1 cells, PKC-beta retards the differentiation of THP-1 cells into macrophage-like cells. (C) 2000 Elsevier Science Inc. All rights reserved.