Association between activation of phase 2 enzymes and down-regulation of dendritic cell maturation by c9,t11-conjugated linoleic acid

Antioxidant and cytoprotective enzymes (phase 2) exert protective activity against reactive oxygen species (ROS)-induced injury. We have recently shown how the beneficial effects of conjugated linoleic acid (CLA) in a mouse model of an autoimmune disease are parallel with the activation of phase 2 enzymes. In the present study we found that c9,t11-CLA isomer activates cytoprotective enzymes and down-regulates LPS- or gliadin-induced maturation in dendritic cells (DCs) obtained from a murine model of celiac disease.As expected, the enhancement of LPS-induced maturation (increased NFκB p65 nuclear translocation, CD86 expression and decreased CD11c+ cell number) was exacerbated by specific glutathione (GSH) inhibitor (buthionine sulphoximine; BSO). Conversely, the down-regulation of DC maturation by antioxidant N-acetylcysteine (NAC) was associated with the marked increase of intracellular thiol concentration. c9,t11-CLA activation of phase 2 enzymes in mouse DCs was observed first. Next, we found that the significant reduction of LPS- and gliadin-induced DC maturation in cultures pre-treated with c9,t11-CLA improved cellular redox status (decreased ROS and higher antioxidant defenses). Finally, the process of DC maturation triggered by gliadin, in contrast with that exhibited by LPS, was not associated with enhanced NFκB nuclear translocation and pro-inflammatory cytokines synthesis. These results demonstrate that c9,t11-CLA renders DCs more resistant to gliadin- or LPS-induced maturation, thus indicating that a cytoprotective mechanism elicited by c9,t11-CLA may modulate DC responsiveness.