HSP27 as a biomarker for predicting skin irritation in human skin and reconstructed organotypic skin model

Chen, Hongxia; Li, Shuhua; Meng, Tian; Zhang, Lei; Dai, Taoli; Xiang, Qi; Su, Zhijian; Zhang, Qihao; Huang, Yadong

doi:10.1016/j.toxlet.2014.01.043

Cited by 10 publications

(8 citation statements)

References 41 publications

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“…We have also studied other genes, SOD1, CFL1, BMP2 and HSP27 that were previously shown to be upregulated in the presence of sodium lauryl sulfate by DNA array or proteomic analysis242528. However, our results showed that no significant upregulation were observed after treatment with various copper compounds (SI1).…”

Section: Discussionmentioning

confidence: 74%

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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: 74%

“…These genes were previously found to be upregulated in the presence of irritants2428. The fold changes in relative gene expression of treatment cells compared to sterile water treated control cultures were determined following 24 h of treatment.…”

Section: Resultsmentioning

confidence: 99%

Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds

Toh

Tan

et al. 2016

Sci Rep

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“…HSP27 is constitutively expressed in the normal skin and confined mainly to the upper epidermal layer (8). Ultraviolet-B irradiation, heating, irritation with methylparaben and sodium lauryl sulphate induced the expression of HSP27 in human keratinocytes or excised skin (9). These reports suggest the existence of a correlation between environmental stress and HSP27 expression in the skin, and it is speculated that HSP27 may be one of the factors promoting repair responses in inflammation occurring in response to environmental stress, including inflammatory skin diseases, such as AD.…”

mentioning

confidence: 99%

Heat Shock Protein 27 kDa Content in Stratum Corneum Correlates with Severity of Atopic Dermatitis

Niiyama¹,

Yoshino²,

Matsukuma³

et al. 2016

Acta Derm Venerol

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“…The ability of chemicals to cause visible changes such as erythema and edema is evaluated by application on test animals, while the effect of chemicals on cell viability is determined by the MTT [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide] assay (Draize, Woodard, & Calvery, ). Changes in cell morphology, gene expression, and/or protein levels are also utilized to evaluate irritant responses (Chen et al, ). While these methods do not always provide definitive answers, they allow discrimination of irritants from nonirritants (Fentem et al, ).…”

Section: Introductionmentioning

confidence: 99%

Irritating effects of sodium lauryl sulfate on human primary keratinocytes at subtoxic levels of exposure

Choi

Shin

Ahn

et al. 2018

Microscopy Res & Technique

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Chemical agents that can potentially cause skin irritation are typically tested in animal models or in vitro assays of cell viability or cytokine expression. However, these methods do not always provide translatable results and are not sufficiently sensitive for subtoxicity detection. Here, we introduce the mechanical properties of keratinocytes as novel endpoints for the safety assessment of chemical agents at the subtoxicity level. Human primary keratinocytes were treated with various concentrations of sodium lauryl sulfate (SLS) and their biological properties (proliferation, membrane integrity, inflammatory response, and morphology) were observed. Their biomechanical and geometrical parameters (stiffness and surface roughness) were also investigated by atomic force microscopy. Keratinocyte morphophysiological changes and inflammatory responses were significant at ≥25 μM SLS. The keratinocytes became less stiff due to changes in the distribution of F-actin filaments and α-tubulin; these changes were significant even at lower doses of SLS (≤10 μM). The morphophysiological changes of keratinocytes were clearly seen at a relatively high dose of SLS, while the mechanical properties of keratinocytes responded linearly to SLS at lower doses. Therefore, changes in mechanical properties can be used as new endpoints for in vitro toxicity testing with keratinocytes. K E Y W O R D S atomic force microscopy, human primary keratinocyte, irritants, mechanical properties, safety assessment

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HSP27 as a biomarker for predicting skin irritation in human skin and reconstructed organotypic skin model

Cited by 10 publications

References 41 publications

Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds

Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds

Heat Shock Protein 27 kDa Content in Stratum Corneum Correlates with Severity of Atopic Dermatitis

Irritating effects of sodium lauryl sulfate on human primary keratinocytes at subtoxic levels of exposure

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