Details zur Publikation

Referenztyp Zeitschriften
DOI / URL Link
Titel (primär) Proteomics analysis of dendritic cell activation by contact allergens reveals possible biomarkers regulated by Nrf2
Autor Mussotter, F.; Tomm, J.M.; El Ali, Z.; Pallardy, M.; Kerdine-Römer, S.; Götz, M.; von Bergen, M.; Haase, A.; Luch, A.;
Journal / Serie Toxicology and Applied Pharmacology
Erscheinungsjahr 2016
Department MOLSYB;
Band/Volume 313
Sprache englisch;
POF III (gesamt) F11;
Keywords Allergic contact dermatitis; Sensitization; Dendritic cell; Keap1/Nrf2; Proteomics; 2D-PAGE
UFZ Querschnittsthemen RU3;
Abstract Allergic contact dermatitis is a widespread disease with high clinical relevance affecting approximately 20% of the general population. Typically, contact allergens are low molecular weight electrophilic compounds which can activate the Keap1/Nrf2 pathway. We performed a proteomics study to reveal possible biomarkers for dendritic cell (DC) activation by contact allergens and to further elucidate the role of Keap1/Nrf2 signaling in this process. We used bone marrow derived dendritic cells (BMDCs) of wild-type (nrf2+/+) and Nrf2 knockout (nrf2−/−) mice and studied their response against the model contact sensitizers 2,4-dinitrochlorobenzene (DNCB), cinnamaldehyde (CA) and nickel(II) sulfate by 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) in combination with electrospray ionization tandem mass spectrometry (ESI-MS/MS). Sodium dodecyl sulfate (SDS, 100 μM) served as irritant control. While treatment with nickel(II) sulfate and SDS had only little effects, CA and DNCB led to significant changes in protein expression. We found 18 and 30 protein spots up-regulated in wild-type cells treated with 50 and 100 μM CA, respectively. For 5 and 10 μM DNCB, 32 and 37 spots were up-regulated, respectively. Almost all of these proteins were not differentially expressed in nrf2−/− BMDCs, indicating an Nrf2-dependent regulation. Among them proteins were detected which are involved in oxidative stress and heat shock responses, as well as in signal transduction or basic cellular pathways. The applied approach allowed us to differentiate between Nrf2-dependent and Nrf2-independent cellular biomarkers differentially regulated upon allergen-induced DC activation. The data presented might contribute to the further development of suitable in vitro testing methods for chemical-mediated sensitization.
ID 18244
dauerhafte UFZ-Verlinkung
Mussotter, F., Tomm, J.M., El Ali, Z., Pallardy, M., Kerdine-Römer, S., Götz, M., von Bergen, M., Haase, A., Luch, A. (2016):
Proteomics analysis of dendritic cell activation by contact allergens reveals possible biomarkers regulated by Nrf2
Toxicol. Appl. Pharmacol. 313 , 170 - 179