Document Detail


Analysis of interleukin-1alpha (IL-1alpha) and interleukin-8 (IL-8) expression and release in in vitro reconstructed human epidermis for the prediction of in vivo skin irritation and/or sensitization.
MedLine Citation:
PMID:  12781210     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the present study, reconstructed human epidermis (RHE) was used as an in vitro model to discriminate 1-chloro-2,4-dinitrobenzene (DNCB), nickel sulfate (NiSO(4)), oxazolone (OXA), 2,4-dinitrofluorobenzene (DNFB) and 2,4,6-trinitrobenzenesulfonic acid (TNBS) as skin sensitizers from benzalkonium chloride (BC), benzoic acid (BA) and sodium lauryl sulfate (SLS) as skin irritants. Our criteria were (a) the differential IL-1alpha and IL-8 synthesis and release (b) cytotoxicity assessment by MTT assay. When the RHE are topically treated with the sensitizers, very low levels of extra- and intracellular IL-1alpha are observed although they induce significant cytotoxicity. In contrast, they exhibit a sharp maximum of IL-8 release. In the presence of the tested irritants, we observe the inverse cytokine release profile, although they induce dose-dependent cytotoxicity profiles similar to those observed with the sensitizers. Finally, IL-1alpha mRNA upregulation is observed after topical application of both sensitizers and irritants, but only the latter significantly increase extracellular IL-1alpha. In conclusion, our results suggest that the associated determination of IL-8, with IL-1alpha, and MTT conversion are at least necessary to discriminate and classify, in a single assay, irritant and sensitizing agents and represent a potential in vitro alternative to two classical in vivo assays.
Authors:
A Coquette; N Berna; A Vandenbosch; M Rosdy; B De Wever; Y Poumay
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  17     ISSN:  0887-2333     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-06-03     Completed Date:  2004-01-28     Revised Date:  2009-04-10    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  311-21     Citation Subset:  IM    
Affiliation:
Department of Biology, SGS Biopharma S.A., Vieux Chemin du Poète 10, B-1301, Wavre, Belgium. alain_coquette@sgs.com
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MeSH Terms
Descriptor/Qualifier:
Administration, Topical
Animal Testing Alternatives
Biological Assay / methods
Biological Markers / analysis*
Coloring Agents / administration & dosage
Culture Techniques
Epidermis / cytology,  drug effects*
Humans
Interleukin-1 / biosynthesis*,  secretion
Interleukin-8 / biosynthesis*,  secretion
Irritants / toxicity*
Predictive Value of Tests
Skin Irritancy Tests / methods
Tetrazolium Salts / administration & dosage
Thiazoles / administration & dosage
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Coloring Agents; 0/Interleukin-1; 0/Interleukin-8; 0/Irritants; 0/Tetrazolium Salts; 0/Thiazoles; 298-93-1/thiazolyl blue

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