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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2936-2942. Prepublished online as a Blood First Edition Paper on December 1, 2005; DOI 10.1182/blood-2005-06-2314. This Article Full Text (PDF) All Versions of this Article: 2005-06-2314v1 107/7/2936    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 Khine, A. A. Articles by Zhang, H. Search for Related Content PubMed PubMed Citation Articles by Khine, A. A. Articles by Zhang, H. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 9, 2005 Accepted November 20, 2005 Human neutrophil peptides induce interleukin-8 production via P2Y6 signaling pathway Aye Aye Khine, Lorenzo Del Sorbo, Rosanna Vaschetto, Stefanos Voglis, Elizabeth Tullis, Arthur S Slutsky, Gregory P Downey, and Haibo Zhang* Departments of Anaesthesia and Critical Care Medicine, St. Michael's Hospital, Toronto, Ontario, Canada; Interdepartmental Division of Critical Care Medicine, Division of Respirology, Department of Physiology, University of Toronto, Toronto, Ontario, Canada Interdepartmental Division of Critical Care Medicine, Division of Respirology, Department of Physiology, University of Toronto, Toronto, Ontario, Canada * Corresponding author; email: haibo.zhang{at}utoronto.ca. The antimicrobial human neutrophil peptides (HNP) play a pivotal role in innate host defense against a broad spectrum of prokaryotic pathogens. In addition, HNP modulate cellular immune responses by producing the chemokine interleukin-8 (IL-8) in myeloid and epithelial cells and by exerting chemotaxis to T cells, immature dendritic cells and monocytes. However, the mechanisms by which HNP modulate the immune responses in the eukaryotic cells remain unclear. We demonstrated that like adenosine triphosphate (ATP) and uridine diphosphate (UDP), HNP stimulation of human lung epithelial cells selectively induced IL-8 production out of 10 pro- and anti-inflammatory cytokines examined. The HNP-induced IL-8 release was inhibited by treatment with the nucleotide receptor antagonists suramin and reactive blue. Transfection of lung epithelial cells with antisense oligonucleotides targeting specific purinergic P2Y receptors revealed that P2Y6 (ligand of UDP) signaling pathway plays a predominant role in mediating HNP-induced IL-8 production. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Theatre, V. Bours, and C. Oury A P2X Ion Channel-Triggered NF-{kappa}B Pathway Enhances TNF-{alpha}-Induced IL-8 Expression in Airway Epithelial Cells Am. J. Respir. Cell Mol. Biol., December 1, 2009; 41(6): 705 - 713. [Abstract] [Full Text] [PDF] O. Soehnlein, L. Lindbom, and C. Weber Mechanisms underlying neutrophil-mediated monocyte recruitment Blood, November 19, 2009; 114(21): 4613 - 4623. [Abstract] [Full Text] [PDF] S. Voglis, K. Quinn, E. Tullis, M. Liu, M. Henriques, C. Zubrinich, O. Penuelas, H. Chan, F. Silverman, V. Cherepanov, et al. Human Neutrophil Peptides and Phagocytic Deficiency in Bronchiectatic Lungs Am. J. Respir. Crit. Care Med., July 15, 2009; 180(2): 159 - 166. [Abstract] [Full Text] [PDF] Y. Jiang, L. Borrelli, B. J. Bacskai, Y. Kanaoka, and J. A. Boyce P2Y6 Receptors Require an Intact Cysteinyl Leukotriene Synthetic and Signaling System to Induce Survival and Activation of Mast Cells J. 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