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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 14, 2004 Accepted August 11, 2004 p38MAPK activation controls the TLR3-mediated upregulation of cytotoxicity and cytokine production in human NK cells Simona Pisegna, Gianluca Pirozzi, Mario Piccoli, Luigi Frati, Angela Santoni, and Gabriella Palmieri* Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci-Bolognetti, University La Sapienza, Rome, Italy Istituto Neurologico Mediterraneo, Pozzilli, Italy * Corresponding author; email: gabriella.palmieri{at}uniroma1.it. 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 upregulate 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 upregulates 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 IFN production induced by either adaptive or innate cytokines. Accordingly with the expression of TLR3 receptor and of TRIF/TICAM-1 adaptor, Poly I:C stimulation induces the activation of IRF-3 transcription factor and of p38 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 signalling and functional events closely correlates with the TLR3 mRNA profile 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. Poly I:C-Induced Activation of NK Cells by CD8{alpha}+ Dendritic Cells via the IPS-1 and TRIF-Dependent Pathways J. Immunol., August 15, 2009; 183(4): 2522 - 2528. [Abstract] [Full Text] [PDF] A. 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