The Use of Human Keratinocytes and Human Skin Models for Predicting Skin Irritation

Sandt, J. van de; Roguet, R.; Cohen, C.; Esdaile, David J.; Ponec, Maria; Corsini, Emanuela; Barker, C.L.; Fusenig, Norbert E.; Liebsch, Manfred; Benford, Diane; Fraissinette, Anne de Brugerolle de; Fartasch, Manigé

doi:10.1177/026119299902700504

Cited by 55 publications

(27 citation statements)

References 79 publications

(63 reference statements)

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“…Besides, in vitro cytotoxicity with HaCaT keratinocytes and human in vivo data was well- correlated223233. HaCaT keratinocytes have also been proven to be good candidates for assessing skin irritancy and toxicity in conventional monolayer assays measuring using MTT reduction as the viability endpoint21.…”

Section: Discussionmentioning

confidence: 92%

“…Keratinocytes make up 95% of the cells in the epidermis and play an integral role in regulating skin irritation. It was found that human keratinocyte cell line closely resembles normal keratinocytes in their growth and differentiation characteristics, hence allowing accurate prediction of response after treatment2122. After exposure to an irritant, the irritant will exert toxic effects on keratinocytes.…”

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confidence: 99%

“…Currently, endpoint measurements are related to severe cell damage such as tetrazolium reduction assay and lactate dehydrogenase (LDH) assay to detect viable cells and IL-1α release as inflammatory markers21. Important early changes occur before severe cell damage take place but no universal markers have yet been identified21.…”

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confidence: 99%

“…Important early changes occur before severe cell damage take place but no universal markers have yet been identified21. The search for new endpoints is necessary, given the complexity of skin irritation mechanism.…”

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confidence: 99%

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Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds

Toh

Tan

et al. 2016

Sci Rep

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Copper is an essential mineral and plays important roles in skin growth and activity. Copper delivery through skin can provide beneficial effects but its potential to induce skin irritation reactions is often overlooked. Data on dermal toxicity caused by copper compounds is scant. Some recognized in vitro skin toxicity methods are unsuitable for all metal compounds. Here, we employ a keratinocyte-based model and evaluated the skin irritation potential of copper compounds at cellular, genomic and proteomic levels. We determined cell viability and cytotoxicity by using tetrazolium reduction assay and Lactate Dehydrogenase (LDH) assay, performed real-time PCR and protein quantification to assess the expression of biomarkers after treating cells with copper peptide (GHK-Cu), copper chloride (CuCl2) and copper acetate (Cu(OAc)2). These copper compounds exhibited different irritancy potentials at the same treatment concentrations. GHK-Cu was not cytotoxic and did not induce any significant change in the expression levels of various skin irritation-related biomarkers. IL-1α and IL-8, HSPA1A and FOSL1 were significantly upregulated following 24-h treatment with CuCl2 and Cu(OAc)2 at 58 and 580 μM without concomitant inhibition in cell viability. GHK-Cu has a low potential of inducing skin irritation and therefore provides a safer alternative for the delivery of copper through skin.

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Section: Discussionmentioning

confidence: 92%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds

Toh

Tan

et al. 2016

Sci Rep

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“…Fibroblasts and keratinocytes are a biologically relevant target for skin irritants (Van de Sandt et al, 1999;Lee et al, 2000).…”

Section: Cytotoxicity In 3t3 Fibroblasts and Hacat Keratinocytesmentioning

confidence: 99%

In vitro study of the cytotoxicity and antiproliferative effects of surfactants produced by Sphingobacterium detergens

Burgos‐Díaz

Martín‐Venegas

Martı́nez

et al. 2013

International Journal of Pharmaceutics

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Kiwi fruit (Actinidia chinensis L.) polysaccharides exert stimulating effects on cell proliferation via enhanced growth factor receptors, energy production, and collagen synthesis of human keratinocytes, fibroblasts, and skin equivalents

Deters¹,

Schröder

Hensel³

2004

Journal Cellular Physiology

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Within physiological engineering exogenous carbohydrates were recently confirmed as pharmacologically active compounds. To investigate potential dermatological activity purified polysaccharides from kiwi fruits (Actinidia chinensis L., Actinidiaceae) were characterized concerning monomer composition, linkage types and molecular weights and were tested under in vitro conditions for regulating activities on cell physiology of human keratinocytes, fibroblasts, and skin equivalents. Ten micrograms per milliliter of raw polysaccharide, neutral type-II-arabinogalactans, and acidic arabinorhamnogalacturonans of kiwi fruits stimulated cell proliferation of human keratinocytes (NHK, HaCaT) up to 30% significantly while mitochondrial activity was stimulated for nearly 25% in regard to control cells. Fibroblasts were not as sensitive as keratinocytes but >130 microg/ml kiwi fruit polysaccharides increased proliferation and ATP-synthesis significantly, too. Proliferation-stimulating activity was dependent on terminal 1-alpha-l-arabinose residues since enzymatic release of these sugar moieties caused significantly decreased proliferation of HaCaT and fibroblasts of about 10% in regard to untreated cells. In three dimensional skin equivalents, it was shown that the polysaccharides led to a doubled collagen synthesis of fibroblasts compared to the normally strongly reduced biosynthetic activity.

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The Use of Human Keratinocytes and Human Skin Models for Predicting Skin Irritation

Cited by 55 publications

References 79 publications

Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds

Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds

In vitro study of the cytotoxicity and antiproliferative effects of surfactants produced by Sphingobacterium detergens

Kiwi fruit (Actinidia chinensis L.) polysaccharides exert stimulating effects on cell proliferation via enhanced growth factor receptors, energy production, and collagen synthesis of human keratinocytes, fibroblasts, and skin equivalents

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