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Prepublished online as a Blood First Edition Paper on May 22, 2003; DOI 10.1182/blood-2002-09-2960. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-09-2960v1 102/6/2259    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 Choi, M. Articles by Kettritz, R. Search for Related Content PubMed PubMed Citation Articles by Choi, M. Articles by Kettritz, R. Related Collections Phagocytes Apoptosis Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 September 2003, Vol. 102, No. 6, pp. 2259-2267 PHAGOCYTES Inhibition of NF-B by a TAT-NEMO–binding domain peptide accelerates constitutive apoptosis and abrogates LPS-delayed neutrophil apoptosis Mira Choi, Susanne Rolle, Maren Wellner, M. Cristina Cardoso, Claus Scheidereit, Friedrich C. Luft, and Ralph Kettritz From the HELIOS Klinikum-Berlin, Franz Volhard Clinic, and Max Delbrück Center for Molecular Medicine, Medical Faculty of the Charité, Humboldt University of Berlin, Berlin, Germany. Delivery of biologically active peptides into human polymorphonuclear neutrophils (PMNs) has implications for studying cellular functions and may be therapeutically relevant. The transcription factor nuclear factor-B (NF-B) regulates the expression of multiple genes controlling inflammation, proliferation, and cell survival. PMNs play a crucial role in first-line defense. Targeting NF-B in these cells may promote apoptosis and therefore facilitate resolution of inflammation. We used an 11-amino acid sequence NEMO-binding domain (NBD) that selectively inhibits the IKK (NEMO)/IKK interaction, preventing NF-B activation. An HIV-TAT sequence served as a highly effective transducing shuttle. We show that lipopolysaccharide (LPS), granulocyte-macrophage colony-stimulating factor (GM-CSF), and dexamethasone (DEX) significantly reduced apoptosis after 20 hours. LPS, but not GM-CSF or DEX, activated NF-B as shown by IB degradation, NF-B DNA binding, and transcriptional activity. The TAT-NBD blocked LPS-induced NF-B activation and NF-B–dependent gene expression. TAT-NBD accelerated constitutive PMN apoptosis dose dependently and abrogated LPS-delayed apoptosis. These results provide a proof of principle for peptide delivery by TAT-derived protein transduction domains to specifically inhibit NF-B activity in PMNs. This strategy may help in controlling various cellular functions even in short-lived, transfection-resistant primary human cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Rahman Review: Antioxidant therapeutic advances in COPD Therapeutic Advances in Respiratory Disease, December 1, 2008; 2(6): 351 - 374. [Abstract] [PDF] C. H.A. Nijboer, C. J. Heijnen, F. Groenendaal, M. J. May, F. van Bel, and A. Kavelaars Strong Neuroprotection by Inhibition of NF-{kappa}B After Neonatal Hypoxia-Ischemia Involves Apoptotic Mechanisms but Is Independent of Cytokines Stroke, July 1, 2008; 39(7): 2129 - 2137. [Abstract] [Full Text] [PDF] M. Choi, B. Salanova, S. Rolle, M. Wellner, W. Schneider, F. C. Luft, and R. 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