SEARCH:   Advanced

Blood, 1 May 2007, Vol. 109, No. 9, pp. 3767-3775. Prepublished online as a Blood First Edition Paper on January 18, 2007; DOI 10.1182/blood-2006-07-037846. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-07-037846v1 109/9/3767    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 Chiossone, L. Articles by Mingari, M. C. Search for Related Content PubMed PubMed Citation Articles by Chiossone, L. Articles by Mingari, M. C. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Molecular analysis of the methylprednisolone-mediated inhibition of NK-cell function: evidence for different susceptibility of IL-2– versus IL-15–activated NK cells Laura Chiossone1, Chiara Vitale2, Francesca Cottalasso2, Sara Moretti1, Bruno Azzarone3, Lorenzo Moretta1,2,4, and Maria Cristina Mingari2,5 1 Istituto Scientifico Giannina Gaslini, Genova, Italy; 2 Dipartimento Medicina Sperimentale, Università di Genova, Genova, Italy; 3 U542 Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Paul Brousse, Villejuif, France; 4 Centro di Eccellenza per le Ricerche Biomedicali, Università di Genova, Genova, Italy; 5 Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy Steroids have been shown to inhibit the function of fresh or IL-2–activated natural killer (NK) cells. Since IL-15 plays a key role in NK-cell development and function, we comparatively analyzed the effects of methylprednisolone on IL-2– or IL-15–cultured NK cells. Methylprednisolone inhibited the surface expression of the major activating receptors NKp30 and NKp44 in both conditions, whereas NK-cell proliferation and survival were sharply impaired only in IL-2–cultured NK cells. Accordingly, methylprednisolone inhibited Tyr phosphorylation of STAT1, STAT3, and STAT5 in IL-2–cultured NK cells but only marginally in IL-15–cultured NK cells, whereas JAK3 was inhibited under both conditions. Also, the NK cytotoxicity was similarly impaired in IL-2– or IL-15–cultured NK cells. This effect strictly correlated with the inhibition of ERK1/2 Tyr phosphorylation, perforin release, and cytotoxicity in a redirected killing assay against the FcR+ P815 target cells upon cross-linking of NKp46, NKG2D, or 2B4 receptors. In contrast, in the case of CD16, inhibition of ERK1/2 Tyr phosphorylation, perforin release, and cytotoxicity were not impaired. Our study suggests a different ability of IL-15–cultured NK cells to survive to steroid treatment, thus offering interesting clues for a correct NK-cell cytokine conditioning in adoptive immunotherapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A.-H. Pillet, F. Bugault, J. Theze, L. A. Chakrabarti, and T. Rose A Programmed Switch from IL-15- to IL-2-Dependent Activation in Human NK Cells J. Immunol., May 15, 2009; 182(10): 6267 - 6277. [Abstract] [Full Text] [PDF] C. Vitale, F. Cottalasso, E. Montaldo, L. Moretta, and M. C. Mingari Methylprednisolone induces preferential and rapid differentiation of CD34+ cord blood precursors toward NK cells Int. Immunol., April 1, 2008; 20(4): 565 - 575. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020