Transduction of the IFN-γ signal for HLA-DR expression in the promonocytic line THP-1 involves a late-acting PKC activity

Richard J. Gumina, Jose Freire-Moar, Lawrence DeYoung, David R. Webb, Bruce H. Devens

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Interferon γ (IFN-γ) is the most potent known lymphokine for activating macrophages and has been shown to induce expression of HLA-DR in THP-1 cells, a monocytic tumor cell line which expresses many of the properties of monocytes, in a dose- and time-dependent manner. Experiments were designed to examine, by FACS analysis and by measurement of messenger RNA levels, the molecular mechanism regulating the expression of HLA-DR molecules. The expression of HLA-DR molecules induced by IFN-γ was blocked by the protein kinase C (PKC) inhibitors sphingosine, staurosporine, and H7. H7 when added up to 20 hr after the initial stimulation with IFN-γ prevented the further expression of HLA-DR. The general kinase inhibitors H8, H9, and HA1004, all less potent PKC inhibitors than H7, did not block the IFN-γ-induced expression of HLA-DR at the concentrations employed. W7, a calmodulin antagonist, but not a PKC inhibitor, was also unable to prevent the IFN-γ-induced expression of HLA-DR. Treatment of THP-1 with phorbol 12-myristate 13-acetate (PMA), a direct activator of PKC, alone or with Ca2+ ionophore A23187, was unable to induce HLA-DR expression. However, pretreatment with PMA for 24 hr prior to IFN-γ stimulation decreased the IFN-γ-induced expression of HLA-DR without decreasing IFN-γ receptor levels. These results suggest that PKC plays a significant role in the IFN-γ-induced signal transduction pathway leading to the expression of HLA-DR in cells of the mononuclear phagocytic lineage, and that PKC activity is required throughout the course of events leading to the actual expression of HLA-DR.

Original languageEnglish (US)
Pages (from-to)265-279
Number of pages15
JournalCellular Immunology
Volume138
Issue number2
DOIs
StatePublished - Dec 1991

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HLA-DR Antigens
Protein Kinase C
Signal Transduction
Protein C Inhibitor
Protein Kinase Inhibitors
Acetates
Sphingosine
Staurosporine
Lymphokines
Ionophores
Calcimycin
Calmodulin
Phagocytes
Tumor Cell Line
Interferons
Monocytes
Phosphotransferases
Macrophages
Messenger RNA

ASJC Scopus subject areas

  • Immunology

Cite this

Transduction of the IFN-γ signal for HLA-DR expression in the promonocytic line THP-1 involves a late-acting PKC activity. / Gumina, Richard J.; Freire-Moar, Jose; DeYoung, Lawrence; Webb, David R.; Devens, Bruce H.

In: Cellular Immunology, Vol. 138, No. 2, 12.1991, p. 265-279.

Research output: Contribution to journalArticle

Gumina, Richard J. ; Freire-Moar, Jose ; DeYoung, Lawrence ; Webb, David R. ; Devens, Bruce H. / Transduction of the IFN-γ signal for HLA-DR expression in the promonocytic line THP-1 involves a late-acting PKC activity. In: Cellular Immunology. 1991 ; Vol. 138, No. 2. pp. 265-279.
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