DNFB activates MAPKs and upregulates CD40 in skin-derived dendritic cells

Matos, Teresa J.; Duarte, Carlos B.; Gonçalo, Margarida; Lopes, María Celeste

doi:10.1016/j.jdermsci.2005.03.011

Cited by 29 publications

(32 citation statements)

References 49 publications

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“…Accordingly, it was previously demonstrated by us and other authors that LPS and skin sensitizers activate MAPK signalling pathways in DC [4,31,37,40,57]. In addition, MAPK are involved in the induction of Nrf2/ARE-dependent gene expression [66].…”

Section: Introductionmentioning

confidence: 91%

Effect of lipopolysaccharide, skin sensitizers and irritants on thioredoxin-1 expression in dendritic cells: relevance of different signalling pathways

et al. 2009

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Thioredoxin-1 is a ubiquitous protein involved in phenotypical and functional changes in dendritic cells (DC). We investigated the eVect of lipopolysaccharide (LPS), skin sensitizers, and irritants on thioredoxin-1 by Western blot and immunoXuorescence 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 eVect observed for LPS (63 § 15%). To address the involvement of thioredoxin-1 in DC maturation, we analysed the eVect 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 veriWed that LPS-induced upregulation of thioredoxin-1 expression was dependent on PI3K pathway.

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Section: Introductionmentioning

confidence: 91%

Effect of lipopolysaccharide, skin sensitizers and irritants on thioredoxin-1 expression in dendritic cells: relevance of different signalling pathways

et al. 2009

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“…In contrast to other DC lines used for studying skin sensitisation hazards, FSDC have the advantage of being cultured in the absence of exogenous recombinant growth factors. We observed that the sensitisers, 2,4-dinitrofluorobenzene (DNFB) and nickel, increased the expression of the membrane-associated proteins CD40 and interleukin (IL) 12 receptor, whereas the non/very weak skin sensitiser 2,4-dichloronitrobenzene (DCNB) did not affect the expression of either protein (Vital et al, 2004;Matos et al, 2005a). Recently, we also found that the CXCR4 chemokine receptor is selectively modulated by skin sensitisers (and not by irritants) in FSDC (Neves et al, 2008).…”

Section: Introductionmentioning

confidence: 98%

Signal transduction profile of chemical sensitisers in dendritic cells: An endpoint to be included in a cell-based in vitro alternative approach to hazard identification?

Neves

Gonçalo

Figueiredo

et al. 2011

Toxicology and Applied Pharmacology

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The development of non-animal testing methods for the assessment of skin sensitisation potential is an urgent challenge within the framework of existing and forthcoming legislation. Efforts have been made to replace current animal tests, but so far no alternative methods have been developed. It is widely recognised that alternatives to animal testing cannot be accomplished with a single approach, but rather will require the integration of results obtained from different in vitro and in silico assays. The argument subjacent to the development of in vitro dendritic cell (DC)-based assays is that sensitiser-induced changes in the DC phenotype can be differentiated from those induced by irritants. This assumption is derived from the unique capacity of DC to convert environmental signals encountered at the skin into a receptor expression pattern (MHC class II molecules, co-stimulatory molecules, chemokine receptors) and a soluble mediator release profile that will stimulate T lymphocytes. Since signal transduction cascades precede changes in surface marker expression and cytokine/ chemokine secretion, these phenotypic modifications are a consequence of a signal transduction profile that is specifically triggered by sensitisers and not by irritants. A limited number of studies have addressed this subject and the present review attempts to summarise and highlight all of the signalling pathways modulated by skin sensitisers and irritants. Furthermore, we conclude this review by focusing on the most promising strategies suitable for inclusion into a cell-based in vitro alternative approach to hazard identification.

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“…Moreover, expressions of major histocompatibility (MHC) class II molecules and costimulatory molecules, such as, CD40, CD54, CD83, and CD86 are upregulated in DCs exposed to contact sensitizers (5-7). Furthermore, contact sensitizers reportedly activate p38 MAP kinase and ERK1/2 in the pathway leading to CD40 upregulation, and these activations are dependent on ROS (reactive oxygen species) (8,9).…”

Section: Introductionmentioning

confidence: 99%

Regulation of macrophage inflammatory protein-2 gene expression in response to 2,4-dinitrofluorobenzene in RAW 264.7 cells

Kim¹,

Kim²,

Kwon³

et al. 2008

BMB Reports

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DNFB activates MAPKs and upregulates CD40 in skin-derived dendritic cells

Abstract: Taken together, these results indicate that the strong sensitizer DNFB activates ERK1/2 and p38 MAPK signaling pathways, and upregulates CD40 protein levels. However, MAPKs do not play a major role in the induction of CD40, one of the phenotypic markers of DC maturation.

Cited by 29 publications

References 49 publications

Effect of lipopolysaccharide, skin sensitizers and irritants on thioredoxin-1 expression in dendritic cells: relevance of different signalling pathways

Effect of lipopolysaccharide, skin sensitizers and irritants on thioredoxin-1 expression in dendritic cells: relevance of different signalling pathways

Signal transduction profile of chemical sensitisers in dendritic cells: An endpoint to be included in a cell-based in vitro alternative approach to hazard identification?

Regulation of macrophage inflammatory protein-2 gene expression in response to 2,4-dinitrofluorobenzene in RAW 264.7 cells

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