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Title: Proteomics analysis of dendritic cell activation by contact allergens reveals possible biomarkers regulated by Nrf2

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{sup +/+}) and Nrf2 knockout (nrf2{sup −/−}) 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{sup −/−} BMDCs, indicating an Nrf2-dependent regulation. Among them proteins were detected which are involved inmore » 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. - Highlights: • Contact allergens induce proteins involved in DC maturation Nrf2-dependently. • Induction of these proteins points to a functional role of Nrf2 in DC maturation. • Evidence that metabolic reprogramming enables DC activation by contact allergens. • Identification of biomarker candidates for development of in vitro testing methods.« less

Authors:
 [1];  [2]; ; ;  [3];  [1];  [2]; ;  [1]
  1. German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Berlin (Germany)
  2. Helmholtz Centre for Environmental Research (UFZ), Department of Molecular Systems Biology, Leipzig (Germany)
  3. INSERM UMR 996, Univ Paris-Sud, Université Paris-Saclay, Chátenay-Malabry (France)
Publication Date:
OSTI Identifier:
22690882
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 313; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ATP; BENZOQUINONES; CYSTEINE; DENDRITES; DERMATITIS; DMSO; FERRITIN; GLUTATHIONE; HEAT-SHOCK PROTEINS; HYDROLASES; INTERFERON; ISOMERASES; KNOCK-OUT REACTIONS; LIGASES; MICE; MITOCHONDRIA; NADP; NICKEL; NICKEL SULFATES; OXYGENASES; PHOSPHOPROTEINS; RECEPTORS; VALIDATION

Citation Formats

Mussotter, Franz, Tomm, Janina Melanie, El Ali, Zeina, Pallardy, Marc, Kerdine-Römer, Saadia, Götz, Mario, Bergen, Martin von, University of Leipzig, Institute of Biochemistry, Leipzig, Aalborg University, Department of Chemistry and Bioscience, Aalborg, Haase, Andrea, and Luch, Andreas. Proteomics analysis of dendritic cell activation by contact allergens reveals possible biomarkers regulated by Nrf2. United States: N. p., 2016. Web. doi:10.1016/J.TAAP.2016.11.001.
Mussotter, Franz, Tomm, Janina Melanie, El Ali, Zeina, Pallardy, Marc, Kerdine-Römer, Saadia, Götz, Mario, Bergen, Martin von, University of Leipzig, Institute of Biochemistry, Leipzig, Aalborg University, Department of Chemistry and Bioscience, Aalborg, Haase, Andrea, & Luch, Andreas. Proteomics analysis of dendritic cell activation by contact allergens reveals possible biomarkers regulated by Nrf2. United States. https://doi.org/10.1016/J.TAAP.2016.11.001
Mussotter, Franz, Tomm, Janina Melanie, El Ali, Zeina, Pallardy, Marc, Kerdine-Römer, Saadia, Götz, Mario, Bergen, Martin von, University of Leipzig, Institute of Biochemistry, Leipzig, Aalborg University, Department of Chemistry and Bioscience, Aalborg, Haase, Andrea, and Luch, Andreas. Thu . "Proteomics analysis of dendritic cell activation by contact allergens reveals possible biomarkers regulated by Nrf2". United States. https://doi.org/10.1016/J.TAAP.2016.11.001.
@article{osti_22690882,
title = {Proteomics analysis of dendritic cell activation by contact allergens reveals possible biomarkers regulated by Nrf2},
author = {Mussotter, Franz and Tomm, Janina Melanie and El Ali, Zeina and Pallardy, Marc and Kerdine-Römer, Saadia and Götz, Mario and Bergen, Martin von and University of Leipzig, Institute of Biochemistry, Leipzig and Aalborg University, Department of Chemistry and Bioscience, Aalborg and Haase, Andrea and Luch, Andreas},
abstractNote = {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{sup +/+}) and Nrf2 knockout (nrf2{sup −/−}) 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{sup −/−} 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. - Highlights: • Contact allergens induce proteins involved in DC maturation Nrf2-dependently. • Induction of these proteins points to a functional role of Nrf2 in DC maturation. • Evidence that metabolic reprogramming enables DC activation by contact allergens. • Identification of biomarker candidates for development of in vitro testing methods.},
doi = {10.1016/J.TAAP.2016.11.001},
url = {https://www.osti.gov/biblio/22690882}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = ,
volume = 313,
place = {United States},
year = {2016},
month = {12}
}