title: Identification of potential biomarkers for predicting acute dermal irritation by proteomic analysis.
abstract: In vitro alternative tests aiming at replacing the traditional animal test for predicting the irritant potential of chemicals have been developed, but the assessment parameters or endpoints are still not sufficient for analysis. To discover novel endpoints for skin irritation responses, a proteomics approach was used to analyze the protein expression in human keratinocytes exposed to sodium lauryl sulfate in the present study. Among the 20 identified proteins with altered expression, small heat shock protein 27 (HSP27) and superoxide dismutase [Cu-Zn] were down-regulated while cofilin-1 was up-regulated significantly in response to the chemical challenge. Keratinocytes were exposed to acid and basic chemicals for further validation of the proteins. HSP27 displayed the most significant alteration both in mRNA and protein levels, accompanied by nuclear translocation. The irritation also induced an increased production of interleukin-1α in keratinocytes. These findings suggest that these proteins may be combinational biomarkers or additional endpoints for skin hazard assessment. Further investigation into the protein alterations would be helpful for the mechanistic understanding of skin irritation.
authors.affiliation: Institute of Life and Health Engineering, and National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, 510632, China.
authors.forename: Qihao
authors.initials: Q
authors.lastname: Zhang
authors.forename: Taoli
authors.initials: T
authors.lastname: Dai
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Minjing
authors.initials: M
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Xiao
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.forename: Ping
authors.initials: P
authors.lastname: Zou
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiang
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Su
authors.forename: Yadong
authors.initials: Y
authors.lastname: Huang
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: He
mesh_terms: D000208:Acute Disease; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured; D051338:Cofilin 1 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism; D007509:Irritants / Q000633:toxicity; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012871:Skin Diseases / Q000139:chemically induced*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C495810:CFL1 protein, human; D051338:Cofilin 1; D055551:HSP27 Heat-Shock Proteins; D053582:Interleukin-1alpha; D007509:Irritants; D013482:Superoxide Dismutase