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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 27, 2006 Accepted December 30, 2006 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 Chiossone, Chiara Vitale*, Francesca Cottalasso, Sara Moretti, Bruno Azzarone, Lorenzo Moretta, and Maria Cristina Mingari Dipartimento Medicina Sperimentale, Universita di Genova, Genova, Italy Centro di Eccellenza per le Ricerche Biomedicali, Universita di Genova, Genova, Italy Dipartimento di Oncologia Biologia e Genetica, Universita di Genova, Genova, Italy Istituto Scientifico Giannina Gaslini, Genova, Italy U542 Institut National de la Sante et de la Recherche Medicale (INSERM), Hopital Paul Brousse, Villejuif, France Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy * Corresponding author; email: chiara_vitale{at}hotmail.com. Steroids have been shown to inhibit the function of fresh or IL-2-activated NK cells. Since IL-15 plays a key role in the 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, while 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 but only marginally in IL-15-cultured NK cells, while 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 crosslinking of NKp46, NKG2D or 2B4 receptors. In contrast, in the case of CD16, neither inhibition of ERK1/2 Tyr-phosphorylation nor perforin release nor cytotoxicity were 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 cells 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]

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