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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4157-4164. Prepublished online as a Blood First Edition Paper on August 17, 2004; DOI 10.1182/blood-2004-05-1860. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-05-1860v1 104/13/4157    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 Pisegna, S. Articles by Palmieri, G. Search for Related Content PubMed PubMed Citation Articles by Pisegna, S. Articles by Palmieri, G. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY p38 MAPK activation controls the TLR3-mediated up-regulation of cytotoxicity and cytokine production in human NK cells Simona Pisegna, Gianluca Pirozzi, Mario Piccoli, Luigi Frati, Angela Santoni, and Gabriella Palmieri From the Department of Experimental Medicine and Pathology, University "La Sapienza," Rome, Italy; Istituto Pasteur-Fondazione Cenci-Bolognetti, University "La Sapienza," Rome, Italy; and Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy. Natural killer (NK) cells are a component of the innate immunity against viral infections through their rapid cytotoxic activity and cytokine production. Although the synthetic double-stranded (ds) RNA polyinosinic-polycytidylic acid (poly I:C), a mimic of a common product of viral infections, is known to rapidly up-regulate their in vivo functions, NK cell ability to directly respond to dsRNA is still mostly unknown. Our results show that treatment with poly I:C significantly up-regulates both natural and CD16-mediated cytotoxicity of highly purified human NK cells. Poly I:C also induces the novel capability of producing CXCL10 chemokine in human NK cells and synergistically enhances interferon- (IFN-) production induced by either adaptive or innate cytokines. In accordance with the expression of Toll-like receptor-3 (TLR3) and of TRIF/TICAM-1 adaptor, poly I:C stimulation induces the activation of interferon regulatory factor-3 (IRF-3) transcription factor and of p38 mitogen-activated protein kinase (MAPK) in human NK cells. Finally, we demonstrate that p38 MAPK activity is required for the dsRNA-dependent enhancement of cytotoxicity and CXCL10 production. The occurrence of dsRNA-induced signaling and functional events closely correlates with the TLR3 mRNAprofile in different NK cell populations. Taken together, these data identify p38 as a central component of NK cell ability to directly respond to dsRNA pathogen-associated molecular pattern (PAMP). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Ma and A. C. Ross Toll-Like Receptor 3 Ligand and Retinoic Acid Enhance Germinal Center Formation and Increase the Tetanus Toxoid Vaccine Response Clin. Vaccine Immunol., October 1, 2009; 16(10): 1476 - 1484. [Abstract] [Full Text] [PDF] T. Miyake, Y. Kumagai, H. Kato, Z. Guo, K. Matsushita, T. Satoh, T. Kawagoe, H. Kumar, M. H. Jang, T. Kawai, et al. 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