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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3285-3293. Prepublished online as a Blood First Edition Paper on July 22, 2004; DOI 10.1182/blood-2004-03-0900. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-0900v1 104/10/3285    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 Taguchi, Y. Articles by Okazaki, T. Search for Related Content PubMed PubMed Citation Articles by Taguchi, Y. Articles by Okazaki, T. Related Collections Immunobiology Apoptosis Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Interleukin-2-induced survival of natural killer (NK) cells involving phosphatidylinositol-3 kinase-dependent reduction of ceramide through acid sphingomyelinase, sphingomyelin synthase, and glucosylceramide synthase Yoshimitsu Taguchi, Tadakazu Kondo, Mitsumasa Watanabe, Michihiko Miyaji, Hisanori Umehara, Yasunori Kozutsumi, and Toshiro Okazaki From the Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; the Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Kyoto, Japan; and the Department of Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Interleukin 2 (IL-2) rescued human natural killer (NK) KHYG-1 cells from apoptosis along with a reduction of ceramide. Conversely, an increase of ceramide inhibited IL-2-rescued survival. IL-2 deprivation-induced activation of acid sphingomyelinase (SMase) and inhibition of glucosylceramide synthase (GCS) and sphingomyelin synthase (SMS) were normalized by IL-2 supplementation. A phosphatidyl inositol-3 (PI-3) kinase inhibitor, LY294002, inhibited IL-2-rescued survival, but a mitogen-activated protein kinase inhibitor, PD98059, and an inhibitor of Janus tyrosine kinase/signal transducer and activator of transcription pathway, AG490, did not. LY294002 inhibited IL-2-induced reduction of ceramide through activation of acid SMase and inhibition of GCS and SMS, suggesting the positive involvement of PI-3 kinase in ceramide reduction through enzymatic regulation. Indeed, a constitutively active PI-3 kinase enhanced growth rate and ceramide reduction through inhibition of acid SMase and activation of GCS and SMS. Further, LY294002 inhibited IL-2-induced changes of transcriptional level as well as mRNA and protein levels in acid SMase and GCS but did not affect the stability of the mRNAs. These results suggest that PI-3 kinase-dependent reduction of ceramide through regulation of acid SMase, GCS, and SMS plays a role in IL-2-rescued survival of NK cells. (Blood. 2004;104:3285-3293) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H.-F. Bao, Z.-R. Zhang, Y.-Y. Liang, J. J. Ma, D. C. Eaton, and H.-P. Ma Ceramide mediates inhibition of the renal epithelial sodium channel by tumor necrosis factor-{alpha} through protein kinase C Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1178 - F1186. [Abstract] [Full Text] [PDF]

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