Effect of lipopolysaccharide, skin sensitizers and irritants on thioredoxin-1 expression in dendritic cells: relevance of different signalling pathways.
Thioredoxin-1 is a ubiquitous protein involved in phenotypical and functional changes in dendritic cells (DC). We investigated the effect of lipopolysaccharide (LPS), skin sensitizers, and irritants on thioredoxin-1 by Western blot and immunofluorescence and on mRNA by real-time PCR. As DC models, we used a skin DC line and DC derived from human blood monocytes. We observed that all tested chemicals increased thioredoxin-1 expression, which is only transient for irritants, being the strongest effect observed for LPS (63 +/- 15%). To address the involvement of thioredoxin-1 in DC maturation, we analysed the effect of an activator of thioredoxin-1 expression, hydrogen peroxide, on CD86 expression, a marker of DC maturation. We found that hydrogen peroxide increases thioredoxin-1 and CD86 expression reinforcing thioredoxin-1 involvement in DC maturation. Because mitogen-activated protein kinases and PI3K are activated upon DC maturation, we also analysed their involvement in thioredoxin-1 modulation. We verified that LPS-induced upregulation of thioredoxin-1 expression was dependent on PI3K pathway.
Francisco
Vera
V
Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
Neves
Bruno Miguel
BM
Cruz
Maria Teresa
MT
Gonçalo
Margarida
M
Figueiredo
Américo
A
Duarte
Carlos B
CB
Lopes
Maria Celeste
MC
D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007509:Irritants / Q000494:pharmacology*; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013879:Thioredoxins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000943:Antigens, Differentiation; D051940:B7-2 Antigen; D007509:Irritants; D008070:Lipopolysaccharides; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases