Details zur Publikation

Referenztyp Zeitschriften
DOI / URL Link
Titel (primär) Benzo[a]pyrene affects Jurkat T cells in the activated state via the antioxidant response element dependent Nrf2 pathway leading to decreased IL-2 secretion and redirecting glutamine metabolism
Autor Murugaiyan, J.; Rockstroh, M.; Wagner, J.; Baumann, S.; Schorsch, K.; Trump, S.; Lehmann, I.; von Bergen, M.; Tomm, J.M.;
Journal / Serie Toxicology and Applied Pharmacology
Erscheinungsjahr 2013
Department IMMU; METABOX; PROTEOM;
Band/Volume 269
Heft 3
Sprache englisch;
POF III (gesamt) F11; T42;
Keywords Benzo[a]pyrene; Antioxidant response element; Jurkat T cell; 2-DE-DIGE; MTT; MALDI TOF MS
UFZ Querschnittsthemen RU3;
Abstract There is a clear evidence that environmental pollutants, such as benzo[a]pyrene (B[a]P), can have detrimental effects on the immune system, whereas the underlying mechanisms still remain elusive. Jurkat T cells share many properties with native T lymphocytes and therefore are an appropriate model to analyze the effects of environmental pollutants on T cells and their activation. Since environmental compounds frequently occur at low, not acute toxic concentrations, we analyzed the effects of two subtoxic concentrations, 50 nM and 5 μM, on non- and activated cells. B[a]P interferes directly with the stimulation process as proven by an altered IL-2 secretion. Furthermore, B[a]P exposure results in significant proteomic changes as shown by DIGE analysis. Pathway analysis revealed an involvement of the AhR independent Nrf2 pathway in the altered processes observed in unstimulated and stimulated cells. A participation of the Nrf2 pathway in the change of IL-2 secretion was confirmed by exposing cells to the Nrf2 activator tBHQ. tBHQ and 5 μM B[a]P caused similar alterations of IL-2 secretion and glutamine/glutamate metabolism. Moreover, the proteome changes in unstimulated cells point towards a modified regulation of the cytoskeleton and cellular stress response, which was proven by western blotting. Additionally, there is a strong evidence for alterations in metabolic pathways caused by B[a]P exposure in stimulated cells. Especially the glutamine/glutamate metabolism was indicated by proteome pathway analysis and validated by metabolite measurements. The detrimental effects were slightly enhanced in stimulated cells, suggesting that stimulated cells are more vulnerable to the environmental pollutant model compound B[a]P.
ID 13671
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=13671
Murugaiyan, J., Rockstroh, M., Wagner, J., Baumann, S., Schorsch, K., Trump, S., Lehmann, I., von Bergen, M., Tomm, J.M. (2013):
Benzo[a]pyrene affects Jurkat T cells in the activated state via the antioxidant response element dependent Nrf2 pathway leading to decreased IL-2 secretion and redirecting glutamine metabolism
Toxicol. Appl. Pharmacol. 269 (3), 307 - 316