Tyrosine phosphorylation pathway is involved in interferon-gamma (IFN-γ) production; effect of sodium ortho vanadate

A. Giovannetti, A. Aiuti, P. M. Pizzoli, M. Pierdominici, E. Agostini, A. Oliva, F. Dianzani, F. Aiuti, F. Pandolfi

Research output: Contribution to journalArticlepeer-review

Abstract

The molecular mechanisms regulating IFN-γ production have yet to be well characterized. We describe here how treatment of activated cultures of peripheral blood mononuclear cells (PBMC) with the phosphotyrosine phosphatases (PTP) inhibitor sodium ortho vanadate results in greatly enhanced IFN-γ production. Conversely, cellular proliferation of the same cultures is profoundly inhibited by treatment with vanadate, while the expression of IL-2R and DR molecules on activated lymphocytes remains substantially unmodified. Increased IFN-γ production, but not inhibition of cellular proliferation, was also observed in mitogen-activated vanadate-treated Jurkat cells. On the other hand, IFN-γ production induced in cultures of PBMC treated or not with vanadate, was strongly inhibited by incubation with the protein tyrosine kinase (PTK) inhibitor herbimycin A. As a result of the inhibited phosphatase activity, substrates for PTK become hyperphosphorylated on tyrosine residues, as shown by Western blot analysis of cell lysates from cultures of PBMC treated with vanadate. We suggest that the tyrosine phosphorylation pathway plays a role in regulating IFN-γ production.

Original languageEnglish
Pages (from-to)157-163
Number of pages7
JournalClinical and Experimental Immunology
Volume100
Issue number1
Publication statusPublished - 1995

Keywords

  • IFN-γ
  • Protein tyrosin phosphatase
  • Protein tyrosine kinase
  • Vanadate

ASJC Scopus subject areas

  • Immunology

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