The gene expression and immunohistochemical time-course of diphenylcyclopropenone induced contact allergy in healthy humans following repeated epicutaneous challenges
| Autor: | Mads A. Røpke, Mads Thomassen, Mark Burton, Ole Clemmensen, Bjarne Winther Kristensen, Torben A Kruse, Flemming Andersen, Peter S. Friedmann, Qihua Tan, Lone Skov, Klaus Ejner Andersen, Kristian Fredløv Mose, Thomas Litman |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Cyclopropanes Time Factors Microarray time-course analysis Biopsy Gene Expression Biochemistry Transcriptome 030207 dermatology & venereal diseases chemistry.chemical_compound 0302 clinical medicine Gene expression Medicine Skin/metabolism Dermatitis Allergic Contact/etiology transcriptional profiling Skin Diphenylcyclopropenone Oligonucleotide Array Sequence Analysis de novo sensitization Interleukin-17 Healthy Volunteers Dermatitis Allergic Contact Immunohistochemistry Female Interleukin-1/metabolism microarray Adult medicine.medical_specialty rechallenge Dermatology Real-Time Polymerase Chain Reaction Interferon-gamma 03 medical and health sciences Young Adult Journal Article Humans Th17 Cells/immunology Th1 Cells/immunology Molecular Biology Gene Interferon-gamma/metabolism business.industry Microarray analysis techniques Gene Expression Profiling Th1 Cells 030104 developmental biology chemistry Interleukin-17/metabolism Immunology Th17 Cells Histopathology business Interleukin-1 |
| Zdroj: | Mose, K F, Burton, M, Thomassen, M, Andersen, F, Kruse, T A, Tan, Q, Skov, L, Almose Røpke, M, Litman, T, Clemmensen, O, Kristensen, B W, S. Friedmann, P & Andersen, K E 2017, ' The gene expression and immunohistochemical time-course of diphenylcyclopropenone induced contact allergy in healthy humans following repeated epicutaneous challenges ', Experimental Dermatology, vol. 26, no. 10, pp. 926–933 . https://doi.org/10.1111/exd.13345 |
| DOI: | 10.1111/exd.13345 |
| Popis: | The gene expression time-course of repeated challenge of contact allergy (CA) remains largely unknown. Therefore, using diphenylcyclopropenone (DPCP) as model allergen in healthy humans we set out to examine: (i) the monotonous and complex gene expression time-course trajectories following repeated DPCP challenges to find the predominant gene expression pattern, (ii) the time-course of cell infiltration following repeated DPCP challenges and (iii) the transcriptome of a repeated CA exposure model. We obtained punch biopsies from control and DPCP-exposed skin from ten DPCP sensitized individuals at 5-6 monthly elicitation challenges. Biopsies were used for microarray gene expression profiling, histopathology and immunohistochemical staining. Validation of microarray data by qRT-PCR was performed on 15 selected genes. Early gene expression time points were also validated in an independent data set. An increasing and decreasing trend in gene expression followed by a plateau was predominantly observed during repeated DPCP challenges. Immune responses reached a plateau after two challenges histopathologically, immunohistochemically and in the time-course gene expression analysis. Transcriptional responses over time revealed a Th1/Th17 polarization as three upstream regulators (IFN-γ, IL-1 and IL-17) activated most of the top upregulated genes. Of the latter genes, 9 of 10 were the same throughout the time course. Excellent correlations between array and PCR data were observed. The transcriptional responses to DPCP over time followed a monotonous pattern. This response pattern confirms and supports the newly reported clinical time-course observations in de novo-sensitized individuals showing a plateau response, and thus, there is concordance between clinical response, histopathology, immunohistochemistry and microarray gene expression in volunteers de novo-sensitized to DPCP. |
| Databáze: | OpenAIRE |
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