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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 (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 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-Carino, J. Search for Related Content PubMed PubMed Citation Articles by Pekkari, K. Articles by Avila-Carino, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 27, 2004 Accepted October 6, 2004 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 T Goodarzi, Annika Scheynius, Arne Holmgren, and Javier Avila-Carino* Department of Biochemistry and Biophysics, Medical Nobel Institute for Biochemistry, Karolinska Institutet, Stockholm, Sweden Department of Medicine, Clinical Allergy Research Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden * Corresponding author; email: Javier.Avila-Carino{at}mbb.ki.se. 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 GM-CSF and IL-4 in that both these cell populations exhibit increased proportions of CD1a+ and mannose receptor (MR)+ cells. However, in contrast to iDC, TAMs express high proportion of CD14 and lower proportion of CD83 and HLA-DR. Functional assays revealed that, in comparison to iDCs, TAMs i) exhibit a higher pinocytic capacity; ii) release significantly higher amounts of the pro-inflammatory cytokines TNF, IL-1 and IL-6 and of the anti-inflammatory cytokine IL-10; and iii) induce a significantly lower proliferative response in allogeneic 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 MAP kinase signaling pathway revealed that Trx80 induces phosphorylation of p38, Erk and 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: J. Bernal-Bayard and F. Ramos-Morales Salmonella Type III Secretion Effector SlrP Is an E3 Ubiquitin Ligase for Mammalian Thioredoxin J. Biol. Chem., October 2, 2009; 284(40): 27587 - 27595. [Abstract] [Full Text] [PDF] T. N. Milovanova, V. M. Bhopale, E. M. Sorokina, J. S. Moore, T. K. Hunt, M. Hauer-Jensen, O. C. Velazquez, and S. R. Thom Hyperbaric oxygen stimulates vasculogenic stem cell growth and differentiation in vivo J Appl Physiol, February 1, 2009; 106(2): 711 - 728. [Abstract] [Full Text] [PDF] T. N. Milovanova, V. M. Bhopale, E. M. Sorokina, J. S. Moore, T. K. Hunt, M. Hauer-Jensen, O. C. Velazquez, and S. R. Thom Lactate Stimulates Vasculogenic Stem Cells via the Thioredoxin System and Engages an Autocrine Activation Loop Involving Hypoxia-Inducible Factor 1 Mol. Cell. Biol., October 15, 2008; 28(20): 6248 - 6261. [Abstract] [Full Text] [PDF] 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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