Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1016/j.taap.2023.116650
Licence creative commons licence
Title (Primary) A comparative proteomics analysis of four contact allergens in THP-1 cells shows distinct alterations in key metabolic pathways
Author Höper, T.; Karkossa, I.; Dumit, V.I.; von Bergen, M.; Schubert, K.; Haase, A.
Source Titel Toxicology and Applied Pharmacology
Year 2023
Department MOLSYB
Volume 475
Page From art. 116650
Language englisch
Topic T9 Healthy Planet
Keywords Allergic contact dermatitis; Proteomics; THP-1 cells; Monocyte-derived dendritic cells; SILAC; LFQ
Abstract Allergic contact dermatitis (ACD) is the predominant form of immunotoxicity in humans. The sensitizing potential of chemicals can be assessed in vitro. However, a better mechanistic understanding could improve the current OECD-validated test battery. The aim of this study was to get insights into toxicity mechanisms of four contact allergens, p-benzoquinone (BQ), 2,4-dinitrochlorobenzene (DNCB), p-nitrobenzyl bromide (NBB) and NiSO4, by analyzing differential proteome alterations in THP-1 cells using two common proteomics workflows, stable isotope labeling by amino acids in cell culture (SILAC) and label-free quantification (LFQ). Here, SILAC was found to deliver more robust results. Overall, the four allergens induced similar responses in THP-1 cells, which underwent profound metabolic reprogramming, including a striking upregulation of the TCA cycle accompanied by pronounced induction of the Nrf2 oxidative stress response pathway. The magnitude of induction varied between the allergens with DNCB and NBB being most potent. A considerable overlap between transcriptome-based signatures of the GARD assay and the proteins identified in our study was found. When comparing the results of this study to a previous proteomics study in human primary monocyte-derived dendritic cells, we found a rather low share in regulated proteins. However, on pathway level, the overlap was high, indicating that affected pathways rather than single proteins are more eligible to investigate proteomic changes induced by contact allergens. Overall, this study confirms the potential of proteomics to obtain a profound mechanistic understanding, which may help improving existing in vitro assays for skin sensitization.
Persistent UFZ Identifier
Höper, T., Karkossa, I., Dumit, V.I., von Bergen, M., Schubert, K., Haase, A. (2023):
A comparative proteomics analysis of four contact allergens in THP-1 cells shows distinct alterations in key metabolic pathways
Toxicol. Appl. Pharmacol. 475 , art. 116650 10.1016/j.taap.2023.116650