Differential Gene Expression Responses Distinguish Contact and Respiratory Sensitizers and Nonsensitizing Irritants in the Local Lymph Node Assay
العنوان: | Differential Gene Expression Responses Distinguish Contact and Respiratory Sensitizers and Nonsensitizing Irritants in the Local Lymph Node Assay |
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المؤلفون: | Darrell R. Boverhof, Michael R. Woolhiser, B. Bhaskar Gollapudi, M. David Adenuga |
المصدر: | Toxicological Sciences. 126:413-425 |
بيانات النشر: | Oxford University Press (OUP), 2012. |
سنة النشر: | 2012 |
مصطلحات موضوعية: | Respiratory System, Real-Time Polymerase Chain Reaction, Toxicology, Mice, Trimellitic anhydride, chemistry.chemical_compound, Gene expression, Dinitrochlorobenzene, medicine, Activation-induced (cytidine) deaminase, Animals, Acrolein, Interleukin 4, Sensitization, Oligonucleotide Array Sequence Analysis, Mice, Inbred BALB C, Dose-Response Relationship, Drug, biology, Chemistry, Local lymph node assay, Gene Expression Profiling, Dendritic cell, Mast cell, medicine.anatomical_structure, Immunology, Irritants, biology.protein, Female, Lymph Nodes |
الوصف: | Genomic approaches have the potential to enhance the specificity and predictive accuracy of existing toxicology endpoints, including those for chemical sensitization. The present study was conducted to determine whether gene expression responses can distinguish contact sensitizers (1-chloro-2,4-dinitrobenzene [DNCB] and hexyl cinnamic aldehyde [HCA]), respiratory sensitizers (ortho-phthalaldehyde and trimellitic anhydride [TMA]), and nonsensitizing irritants (methyl salicylate [MS] and nonanoic acid [NA]) in the local lymph node assay (LLNA). Female Balb/c mice received doses of each chemical as per the standard LLNA dosing regimen on days 1, 2, and 3. Auricular lymph nodes were analyzed for tritiated thymidine ((3)HTdR) incorporation on day 6 and for gene expression responses on days 6 and 10. All chemicals induced dose-dependent increases in stimulation index, which correlated strongly with the number of differentially expressed genes. A majority of genes modulated by the irritants were similarly altered by the sensitizers, consistent with the irritating effects of the sensitizers. However, a select number of responses involved with immune-specific functions, such as dendritic cell activation, were unique to the sensitizers and may offer the ability to distinguish sensitizers from irritants. Genes for the mast cell proteases 1 and 8, Lgals7, Tim2, Aicda, Il4, and Akr1c18 were more strongly regulated by respiratory sensitizers compared with contact sensitizers and may represent potential biomarkers for discriminating between contact and respiratory sensitizers. Collectively, these data suggest that gene expression responses may serve as useful biomarkers to distinguish between respiratory and contact sensitizers and nonsensitizing irritants in the LLNA. |
تدمد: | 1096-0929 1096-6080 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4182f71f46f13d8078aa7eee54ab9b72 https://doi.org/10.1093/toxsci/kfs071 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....4182f71f46f13d8078aa7eee54ab9b72 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 10960929 10966080 |
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