Details zur Publikation
|Titel (primär)||A proteomics approach to elucidate the role of Nrf2 in primary bone-marrow-derived dendritic cells of mice upon activation by contact allergens|
|Autor||Mussotter, F.; Haase, A.; Tomm, J.M.; El Ali, Z.; Kerdine-Römer, S.; Pallardy, M.; von Bergen, M.; Luch, A.|
|Journal / Serie||Toxicology Letters|
Contact sensitizers are low molecular weight compounds, which can prompt dendritic cells in the skin to subsequently activate naïve T-cells in draining lymph nodes. Often these compounds are electrophilic and activate the Keap1/Nrf2 pathway. We aimed to further elucidate the molecular mechanisms of skin sensitization.
We used bone marrow-derived dendritic cells (BMDC) from CD34+ progenitor cells from wild-type or Nrf2−/− mice. Cells were treated for 8 h with different contact allergens: cinnamaldehyde (CA), 1-chloro-2,4-dinitrobenzene (DNCB), nickel sulfate (NiSO4) or with SDS as an irritant control. Analysis was performed using 2D gels and ESI-MS/MS. Ingenuity IPA® was used for pathway analyses.
While treatments with nickel and SDS had only low effects, CA and DNCB led to significant changes in protein expression. Most of these proteins showed no significant regulation in Nrf2−/− cells, indicating an Nrf2-dependent cellular response. We identified several Nrf2-dependent proteins like glutamate cysteine ligase, heme oxygenase or catalase. We also identified other proteins involved in oxidative stress response, signal transduction pathways, basic cellular pathways and heat shock response.
IPA® upstream analysis confirmed activation of Nrf2-related pathways in wild-type but not in knockout cells. Furthermore IPA® predicted Nrf2-dependent activation of pathways regulated by TGFβ, PPARγ and CD38 which are known to play an important role in dendritic cell maturation and function. A more pronounced regulation of glucose metabolism, PI3K/AKT signalling and protein degradation in wildtype cells also indicated Nrf2-dependent BMDC activation. Altogether IPA® predicted an anti-apoptotic, -necrotic and -inflammatory response in wildtype but not in Nrf2−/− cells.
|Mussotter, F., Haase, A., Tomm, J.M., El Ali, Z., Kerdine-Römer, S., Pallardy, M., von Bergen, M., Luch, A. (2014):
A proteomics approach to elucidate the role of Nrf2 in primary bone-marrow-derived dendritic cells of mice upon activation by contact allergens
Toxicol. Lett. 229 (Suppl.), S203