PMID- 15494431
OWN - NLM
STAT- MEDLINE
DCOM- 20050303
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 105
IP  - 4
DP  - 2005 Feb 15
TI  - 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.
PG  - 1598-605
AB  - 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-alpha (TNF alpha), IL-1 beta, 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.
FAU - Pekkari, Klas
AU  - Pekkari K
AD  - Medical Nobel Institute for Biochemistry, Department of Biochemistry and 
      Biophysics, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
FAU - Goodarzi, Mohammad Taghi
AU  - Goodarzi MT
FAU - Scheynius, Annika
AU  - Scheynius A
FAU - Holmgren, Arne
AU  - Holmgren A
FAU - Avila-Carino, Javier
AU  - Avila-Carino J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041019
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Cytokines)
RN  - 0 (Dextrans)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Peptide Fragments)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Trx80 protein, human)
RN  - 52500-60-4 (Thioredoxins)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
SB  - IM
MH  - Cell Differentiation/*immunology
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Dextrans/metabolism
MH  - Endocytosis/immunology
MH  - Enzyme Activation/immunology
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism/physiology
MH  - Fluorescein-5-isothiocyanate/metabolism
MH  - Humans
MH  - Immunophenotyping
MH  - Inflammation Mediators/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/*metabolism/physiology
MH  - Lipopolysaccharide Receptors/*biosynthesis
MH  - Lymphocyte Culture Test, Mixed
MH  - Monocytes/cytology/*enzymology/*immunology/metabolism
MH  - Peptide Fragments/*pharmacology
MH  - Recombinant Proteins/pharmacology
MH  - Thioredoxins/*pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism/physiology
EDAT- 2004/10/21 09:00
MHDA- 2005/03/04 09:00
CRDT- 2004/10/21 09:00
PHST- 2004/10/21 09:00 [pubmed]
PHST- 2005/03/04 09:00 [medline]
PHST- 2004/10/21 09:00 [entrez]
AID - S0006-4971(20)45885-9 [pii]
AID - 10.1182/blood-2004-04-1577 [doi]
PST - ppublish
SO  - Blood. 2005 Feb 15;105(4):1598-605. doi: 10.1182/blood-2004-04-1577. Epub 2004 
      Oct 19.