IGF-1 down-regulates IFN-γR2 chain surface expression and desensitizes IFN-γ/STAT-1 signaling in human T lymphocytes

Paola Bernabei, Marita Bosticardo, Giuliana Losana, Gabriella Regis, Francesca Di Paola, Stefania De Angelis, Mirella Giovarelli, Francesco Novelli

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Abstract

The ability of insulin-like growth factor-1 (IGF-1) to regulate surface expression of the interferon-γ receptor 2 (IFN-γR2) transducing chain and activation of IFN-γ-induced signal transducer and activator of transcriptfon-1 (STAT-1) in human T cells was analyzed. We show that, especially in the absence of serum (which contains IGF-1), IGF-1 down-regulated surface expression of the IFN-γR2 chain and inhibited both IFN-γ-dependent STAT-1 activation and apoptosis in T-cell lines ST4, Jurkat, and Molt-4. IFN-γR2 down-regulation resulted from its enhanced internalization since IGF-1 completely restored the uptake of anti-IFN-γR2 monoclonal antibody (mAb) in serum-deprived T-cell lines. When the interaction between IGF-1 and its receptor was blocked by anti-IGF-1R mAb, enhancement of IFN-γR2 surface expression, STAT-1 activation, and reinstatement of IFN-γ-induced apoptosis were observed. Enhanced expression of IFN-γR2 was also observed in phytohemagglutinin (PHA)-activated T lymphoblasts cultured in the presence of anti-IGF-1R mAb, whereas IGF-1 or anti-IGF-1R mAb did not modify the high IFN-γR2 expression in B and myeloid cell lines. Both IGF-1 and anti-IGF-1R mAb did not modify the constitutive expression of IFN-γR2 mRNA in T cells as well as the high IFN-γR1 binding chain surface expression in T, B, and myeloid cells. These data indicate that IGF-1 plays a critical role in the desensitization of IFN-γ/STAT-1 signaling in T lymphocytes by delivering a signal for IFN-γR2 internalization.

Original languageEnglish
Pages (from-to)2933-2939
Number of pages7
JournalBlood
Volume102
Issue number8
DOIs
Publication statusPublished - Oct 15 2003

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ASJC Scopus subject areas

  • Hematology

Cite this

Bernabei, P., Bosticardo, M., Losana, G., Regis, G., Di Paola, F., De Angelis, S., Giovarelli, M., & Novelli, F. (2003). IGF-1 down-regulates IFN-γR2 chain surface expression and desensitizes IFN-γ/STAT-1 signaling in human T lymphocytes. Blood, 102(8), 2933-2939. https://doi.org/10.1182/blood-2003-01-0100