caa a22 4500 606233741 CHVBK 20210128101233.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s11010-015-2372-8 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2372-8 Tocopherol isoforms (α-, γ-, and δ-) show distinct capacities to control Nrf-2 and NfκB signaling pathways that modulate inflammatory response in Caco-2 intestinal cells [Elektronische Daten] [Ingrid Elisia, David Kitts] We recently showed that α-, γ-, and δ-tocopherols (Toc) were isoform dependent in modulating an inflammatory response in differentiated human Caco-2 intestinal cells. Here, we aim to investigate the relative capacity of Toc isoforms to modify the stress-activated NfκB and Nrf-2 signaling pathways that regulate the expression of pro-inflammatory cytokines and antioxidant enzymes, respectively, in this well-established in vitro model of the small intestine The modulation of IFNγ/phorbol myristate acetate (PMA)-induced inflammatory responses, determined by the expression of IL8 mRNA and protein, corresponded to the extent by which different Toc isoforms altered intracellular oxidative status in Caco-2 cells. α Toc was more effective at suppressing IFNγ/PMA-induced NfκB activation than γ-Toc, while δ-Toc was ineffective. On the other hand, only δ-Toc and to a lesser extent γ-Toc promoted IFNγ/PMA-induced Nrf-2 activation. Up-regulation of Nrf-2 by δ-Toc coincided with a decrease in GSH/GSSG ratio, thus pointing to pro-oxidant activity of δ-Toc isoform in IFNγ/PMA-stimulated Caco-2 cells. The induction of oxidative stress in IFNγ/PMA-treated cells by δ-Toc was lowered (P<0.05) in the presence of ascorbic acid. Ascorbic acid also enabled a greater suppression of IL8 secretion than when cells were treated with δ-Toc isoform alone. Our findings show that δ-Toc uniquely promoted oxidative stress which translated to Toc isoform-specific modulation of the stress-activated Nrf-2 and NfκB signaling pathway and an influence on IL8 expression. Springer Science+Business Media New York, 2015 IL8 nationallicence Nrf-2 nationallicence NfκB nationallicence Tocopherol nationallicence Pro-oxidant nationallicence Inflammation nationallicence Elisia Ingrid Food, Nutrition and Health Program, University of British Columbia, 219-2205 East Mall, V6T 1Z4, Vancouver, BC, Canada aut Kitts David Food, Nutrition and Health Program, University of British Columbia, 219-2205 East Mall, V6T 1Z4, Vancouver, BC, Canada aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 404/1-2(2015-06-01), 123-131 0300-8177 404:1-2<123 2015 404 11010 https://doi.org/10.1007/s11010-015-2372-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2372-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Elisia Ingrid Food, Nutrition and Health Program, University of British Columbia, 219-2205 East Mall, V6T 1Z4, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Kitts David Food, Nutrition and Health Program, University of British Columbia, 219-2205 East Mall, V6T 1Z4, Vancouver, BC, Canada aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 404/1-2(2015-06-01), 123-131 0300-8177 404:1-2<123 2015 404 11010