SEARCH:   Advanced

Blood, 15 October 2003, Vol. 102, No. 8, pp. 2933-2939. Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2003-01-0100. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0100v1 102/8/2933    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bernabei, P. Articles by Novelli, F. Search for Related Content PubMed PubMed Citation Articles by Bernabei, P. Articles by Novelli, F. Related Collections Immunobiology Apoptosis Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY IGF-1 down-regulates IFN-R2 chain surface expression and desensitizes IFN-/STAT-1 signaling in human T lymphocytes Paola Bernabei, Marita Bosticardo, Giuliana Losana, Gabriella Regis, Francesca Di Paola, Stefania De Angelis, Mirella Giovarelli, and Francesco Novelli From the Center for Experimental Research and Medical Studies (CeRMS), San Giovanni Battista Hospital, Turin, Italy; and the Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy. The ability of insulin-like growth factor-1 (IGF-1) to regulate surface expression of the interferon- receptor 2 (IFN-R2) transducing chain and activation of IFN-–induced signal transducer and activator of transcription-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-R2 chain and inhibited both IFN-–dependent STAT-1 activation and apoptosis in T-cell lines ST4, Jurkat, and Molt-4. IFN-R2 down-regulation resulted from its enhanced internalization since IGF-1 completely restored the uptake of anti–IFN-R2 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-R2 surface expression, STAT-1 activation, and reinstatement of IFN-–induced apoptosis were observed. Enhanced expression of IFN-R2 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-R2 expression in B and myeloid cell lines. Both IGF-1 and anti–IGF-1R mAb did not modify the constitutive expression of IFN-R2 mRNA in T cells as well as the high IFN-R1 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-/STAT-1 signaling in T lymphocytes by delivering a signal for IFN-R2 internalization. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. N. Vallejo, J. J. Michel, L. K. Bale, B. H. Lemster, L. Borghesi, and C. A. Conover Resistance to age-dependent thymic atrophy in long-lived mice that are deficient in pregnancy-associated plasma protein A PNAS, July 7, 2009; 106(27): 11252 - 11257. [Abstract] [Full Text] [PDF] R. J. Critchley-Thorne, D. L. Simons, N. Yan, A. K. Miyahira, F. M. Dirbas, D. L. Johnson, S. M. Swetter, R. W. Carlson, G. A. Fisher, A. Koong, et al. Impaired interferon signaling is a common immune defect in human cancer PNAS, June 2, 2009; 106(22): 9010 - 9015. [Abstract] [Full Text] [PDF] L. Conti, G. Regis, A. Longo, P. Bernabei, R. Chiarle, M. Giovarelli, and F. Novelli In the absence of IGF-1 signaling, IFN-{gamma} suppresses human malignant T-cell growth Blood, March 15, 2007; 109(6): 2496 - 2504. [Abstract] [Full Text] [PDF] N. E. Buckley, A. M. Hosey, J. J. Gorski, J. W. Purcell, J. M. Mulligan, D. P. Harkin, and P. B. Mullan BRCA1 Regulates IFN-{gamma} Signaling through a Mechanism Involving the Type I IFNs Mol. Cancer Res., March 1, 2007; 5(3): 261 - 270. [Abstract] [Full Text] [PDF] R. S. Douglas, A. G. Gianoukakis, S. Kamat, and T. J. Smith Aberrant Expression of the Insulin-Like Growth Factor-1 Receptor by T Cells from Patients with Graves' Disease May Carry Functional Consequences for Disease Pathogenesis J. Immunol., March 1, 2007; 178(5): 3281 - 3287. [Abstract] [Full Text] [PDF] C. Leon, D. Nandan, M. Lopez, A. Moeenrezakhanlou, and N. E. Reiner Annexin V Associates with the IFN-{gamma} Receptor and Regulates IFN-{gamma} Signaling J. Immunol., May 15, 2006; 176(10): 5934 - 5942. [Abstract] [Full Text] [PDF] J. Nigro, N. Osman, A. M. Dart, and P. J. Little Insulin Resistance and Atherosclerosis Endocr. Rev., May 1, 2006; 27(3): 242 - 259. [Abstract] [Full Text] [PDF] G. Regis, M. Bosticardo, L. Conti, S. De Angelis, D. Boselli, B. Tomaino, P. Bernabei, M. Giovarelli, and F. Novelli Iron regulates T-lymphocyte sensitivity to the IFN-{gamma}/STAT1 signaling pathway in vitro and in vivo Blood, April 15, 2005; 105(8): 3214 - 3221. [Abstract] [Full Text] [PDF] S. Banerjee, A. Smallwood, J. Moorhead, A. E. Chambers, A. Papageorghiou, S. Campbell, and K. Nicolaides Placental Expression of Interferon-{gamma} (IFN-{gamma}) and Its Receptor IFN-{gamma}R2 Fail to Switch from Early Hypoxic to Late Normotensive Development in Preeclampsia J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 944 - 952. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020