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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1598-1605. Prepublished online as a Blood First Edition Paper on October 19, 2004; DOI 10.1182/blood-2004-04-1577. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1577v1 105/4/1598    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 Pekkari, K. Articles by Avila-Cariño, J. Search for Related Content PubMed PubMed Citation Articles by Pekkari, K. Articles by Avila-Cariño, J. Related Collections Immunobiology Phagocytes Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Truncated thioredoxin (Trx80) induces differentiation of human CD14+ monocytes into a novel cell type (TAMs) via activation of the MAP kinases p38, ERK, and JNK Klas Pekkari, Mohammad Taghi Goodarzi, Annika Scheynius, Arne Holmgren, and Javier Avila-Cariño From the Medical Nobel Institute for Biochemistry, Department of Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; and the Department of Medicine, Clinical Allergy Research Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden. Thioredoxin truncated at its carboxy terminal (Trx80) acts as a cytokine that stimulates monocytes and eosinophils. In the present study, Trx80 was shown to induce differentiation of human CD14+ monocytes into a cell type not described previously, which we designate as Trx80-activated monocytes (TAMs). TAMs resemble immature dendritic cells (iDCs) generated in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) in that both these cell populations exhibit increased proportions of CD1a+ and mannose receptor (MR)+ cells. However, in contrast to iDCs, TAMs express high proportion of CD14 and lower proportion of CD83 and HLA-DR. Functional assays revealed that, in comparison to iDCs, TAMs 1) exhibit a higher pinocytic capacity; 2) release significantly higher amounts of the proinflammatory cytokines tumor necrosis factor- (TNF), IL-1, and IL-6 and of the anti-inflammatory cytokine IL-10; and 3) induce a significantly lower proliferative response in allogeneic peripheral blood mononuclear cells (PBMCs). Indeed, Trx80 appears to be the first endogenous substance shown to have the capacity on its own to induce IL-10 production by monocytes. Analysis of the mitogen-activated protein (MAP) kinase signaling pathway revealed that Trx80 induces phosphorylation of p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). We propose that Trx80 is an early signal in response to danger, and that TAMs may play a major role in triggering innate immune responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Shamaei-Tousi, J. P. Halcox, and B. Henderson Stressing the obvious? Cell stress and cell stress proteins in cardiovascular disease Cardiovasc Res, April 1, 2007; 74(1): 19 - 28. [Abstract] [Full Text] [PDF] B. Henderson, E. Allan, and A. R. M. Coates Stress Wars: the Direct Role of Host and Bacterial Molecular Chaperones in Bacterial Infection Infect. Immun., July 1, 2006; 74(7): 3693 - 3706. [Full Text] [PDF]

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