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

Francisco, Vera; Neves, Bruno Miguel; Cruz, Maria Teresa; Gonçalo, Margarida; Figueiredo, Américo; Duarte, Carlos B.; Lopes, María Celeste

doi:10.1007/s00403-009-0993-z

Cited by 2 publications

(2 citation statements)

References 68 publications

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“…These results showed that electrophilic molecules, including sensitisers, activated the Keap1/Nrf2-signalling pathway in dendritic cells and in the THP-1 cell line. Similarly, it was previously demonstrated that the skin sensitiser nickel activates the Nrf2 signalling pathway in human monocytic cells (Lewis et al, 2006) and our previous work demonstrated that thioredoxin, a protein encoded by a gene containing an ARE element in the promoter region, is involved in DC maturation (Francisco et al, 2010). The effect of dinitrohalobenzenes in Nrf2 was also tested in THP-1 cells, together with several other markers, namely for changes in CD54 levels, IL-8 release, p38 MAPK phosphorylation and NF-kB (Megherbi et al, 2009).…”

Section: Activation Of the Nrf2/are Transcription Factor Signalling Psupporting

confidence: 61%

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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Section: Activation Of the Nrf2/are Transcription Factor Signalling Psupporting

confidence: 61%

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 effect of drugs was studied on intracellular signalling pathways (p38 MAPK) and genes coding for DC maturation markers, pro-inflammatory cytokines/chemokines and cell detoxifying enzymes (CD40, CD83, CD86, CCR7, HMOX1, IL8, IL12B and CXCL10), commonly used for the evaluation of skin sensitizers. Results of systemic drugs on THP-1 cells were compared with LPS, a potent DC maturation stimulus that activates TLR-4, and with DNFB, a very strong contact sensitizer, documented both in vivo and in vitro tests (Pickard et al, 2007;Francisco et al, 2010;Nukada et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Systemic drugs inducing non‐immediate cutaneous adverse reactions and contact sensitizers evoke similar responses in THP‐1 cells

Gonçalo

Martins

Silva

et al. 2014

J of Applied Toxicology

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Contact sensitizers induce phenotypic and functional changes in dendritic cells (DC) that enhance their antigen-presenting capacity and, ultimately, modulate the T cell response. To evaluate if there is a similar effect of drugs causing T-cell-mediated cutaneous adverse drug reactions (CADR), we studied the in vitro effect of drugs on THP-1 cells, a cell line widely used to evaluate the early molecular and cellular events triggered by contact sensitizers. The effect of allopurinol, oxypurinol, ampicillin, amoxicillin, carbamazepine and sodium valproate, at EC30 concentrations, was evaluated on p38 MAPK activation, by Western Blot, and on the expression of genes coding for DC maturation markers, pro-inflammatory cytokine/chemokines and hemeoxygenase 1 (HMOX1), by real-time RT-PCR. Results were compared with lipopolysaccharide (LPS), a DC maturation stimulus, and the strong contact sensitizer, 1-fluoro-2,4-dinitrobenzene (DNFB). All drugs studied significantly upregulated HMOX1 gene transcription and all, except the anticonvulsants, also upregulated IL8. Allopurinol and oxypurinol showed the most intense effect, in a magnitude similar to DNFB and superior to betalactams. Transcription of CD40, IL12B and CXCL10 genes by drugs was more irregular. Moreover, like DNFB, all drugs activated p38 MAPK, although significantly only for oxypurinol. Like contact sensitizers, drugs that cause non-immediate CADR activate THP-1 cells in vitro, using different signalling pathways and affecting gene transcription with an intensity that may reflect the frequency and severity of the CADR they cause. Direct activation of antigen-presenting DC by systemic drugs may be an important early step in the pathophysiology of non-immediate CADR.

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

Cited by 2 publications

References 68 publications

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?

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?

Systemic drugs inducing non‐immediate cutaneous adverse reactions and contact sensitizers evoke similar responses in THP‐1 cells

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