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Blood, 1 March 2006, Vol. 107, No. 5, pp. 2112-2122. Prepublished online as a Blood First Edition Paper on November 3, 2005; DOI 10.1182/blood-2005-01-0428. This Article Full Text (PDF) All Versions of this Article: 2005-01-0428v1 107/5/2112    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 Biswas, S. K Articles by Sica, A. Search for Related Content PubMed PubMed Citation Articles by Biswas, S. K Articles by Sica, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 31, 2005 Accepted October 17, 2005 A distinct and unique transcriptional programme expressed by tumor-associated macrophages: defective NF-B and enhanced IRF-3/STAT1 activation Subhra K Biswas, Lisa Gangi, Saki Paul, Tiziana Schioppa, Alessandra Saccani, Marina Sironi, Barbara Bottazzi, Andrea Doni, Vincenzo Bronte, Fabio Pasqualini, Luca Vago, Manuela Nebuloni, Alberto Mantovani, and Antonio Sica* Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy Laboratory of Molecular Technology, Microarray Research Group, National Cancer Institute-SAIC, Frederick, USA Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; Istituto clinico Humanitas, Milan, Milan, Italy Department of Oncology and Surgical Sciences, Oncology Section, Padua University, Padua, Italy Centro di Eccellenza per I'Innovazione Diagnostica e Terapeutica, State University of Milan, Institute of Pathology, Milan, Italy Department of Clinical Sciences, State University of Milan, Institute of Pathology, Milan, Italy Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; Centro di Eccellenza per I'Innovazione Diagnostica e Terapeutica, State University of Milan, Institute of Pathology, Milan, Italy; Istituto clinico Humanitas, Milan, Milan, Italy * Corresponding author; email: antonio.sica{at}humanitas.it. To identify the molecular basis underlying the functions of Tumor-Associated Macrophages (TAM), we characterized the gene expression profile of TAM isolated from a murine fibrosarcoma in comparison with peritoneal macrophages (PEC) and immature suppressor cells (MSC), using a cDNA microarray technology. Among the differentially expressed genes, 15 genes relevant to inflammation and immunity were validated by real-time PCR and protein production. Resting TAM showed a characteristic gene expression pattern, with higher expression of genes coding for the immunosuppressive cytokine IL-10, phagocytosis-related receptors/molecules (Msr2 and C1q) and inflammatory chemokines (CCL2 and CCL5) as expected, as well as, unexpectedly, IFN-inducible chemokines (CXCL9, CXCL10, CXCL16). Immunohistology confirmed and extended the in vitro analysis by showing that TAM express M2-associated molecules (e.g. IL-10 and MGL1), as well as CCL2, CCL5, CXCL9, CXCL10 and CXCL16, but no appreciable NOS2. Lipopolysaccharide (LPS)-mediated activation of TAM resulted in defective expression of several proinflammatory cytokines (e.g. IL-1, IL-6, TNF-) and chemokines (eg. CCL3), as opposed to a strong up-regulation of immunosuppressive cytokines (IL-10, TGF) and IFN-inducible chemokines (CCL5, CXCL9, CXCL10, CXCL16). The TAM functional profile was associated with defective activation of NF-kB but unexpected activation of MyD88-independent IRF-3 and STAT1.Thus, profiling of TAM from a murine sarcoma revealed unexpected expression of IFN-inducible chemokines, associated with an M2 phenotype (IL-10high, IL-12low), and divergent regulation of the NF-B versus the IRF-3/STAT1 pathway. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. M. Donson, D. K. Birks, V. N. Barton, Q. Wei, B. K. Kleinschmidt-DeMasters, M. H. Handler, A. E. Waziri, M. Wang, and N. K. 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