TY - JOUR
T1 - Tyrosine phosphorylation pathway is involved in interferon-gamma (IFN-γ) production; effect of sodium ortho vanadate
AU - Giovannetti, A.
AU - Aiuti, A.
AU - Pizzoli, P. M.
AU - Pierdominici, M.
AU - Agostini, E.
AU - Oliva, A.
AU - Dianzani, F.
AU - Aiuti, F.
AU - Pandolfi, F.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
KW - IFN-γ
KW - Protein tyrosin phosphatase
KW - Protein tyrosine kinase
KW - Vanadate
UR - http://www.scopus.com/inward/record.url?scp=0028930950&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028930950&partnerID=8YFLogxK
M3 - Article
C2 - 7535209
AN - SCOPUS:0028930950
VL - 100
SP - 157
EP - 163
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
SN - 0009-9104
IS - 1
ER -