Conversion of t11t13 CLA into c9t11 CLA in Caco-2 cells and inhibition by sterculic oil.

BACKGROUND: Conjugated linoleic acids (CLA), and principally c9t11 CLA, are suspected to have numerous preventive properties regarding non-infectious pathologies such as inflammatory diseases, atherosclerosis and several types of cancer. C9t11 CLA is produced in the rumen during biohydrogenation of linoleic acid, but can also be synthesized in mammalian tissues from trans-vaccenic acid (C18:1 t11) through the action of delta-9 desaturase (D9D). For several years, it is also known that c9t11 CLA can be synthesized from conjugated linolenic acids (CLnA), i.e. c9t11c13 CLnA and c9t11t13 CLnA. This study aimed at investigating to which extent and by which route c9t11 CLA can be produced from another isomer of CLA, the t11t13 CLA that is structurally very similar to c9t11t13 CLnA, in Caco-2 cells. METHODOLOGY/PRINCIPAL FINDINGS: Caco-2 cells were incubated for 24 h with 20 µmol/l of t11t13 CLA in the absence or presence of sterculic oil used as an inhibitor of D9D. Caco-2 cells were able to convert t11t13 CLA into c9t11 CLA, and c9t11t13 CLnA was formed as an intermediate compound. In the presence of sterculic oil, the production of this intermediate was decreased by 46% and the formation of c9t11 CLA was decreased by 26%. No other metabolite was detected. CONCLUSIONS/SIGNIFICANCE: These results not only highlight the conversion of t11t13 CLA into c9t11 CLA but demonstrate also that this conversion involves first a desaturation step catalysed by D9D to produce c9t11t13 CLnA and then the action of another enzyme reducing the double bond on the Δ13 position.

Effects of conjugated linoleic acid on growth and cytokine expression in Jurkat T cells.

Conjugated linoleic acid (CLA) has shown beneficial properties in animal models including anti-cancer, anti-atherogenic and anti-diabetic effects, while contrasting immunological effects were reported. While its anti-inflammatory activity has been associated to inhibition of arachidonic acid biosynthesis and to peroxisome proliferator-activated receptors (PPARs) activity, the molecular pathways underlying its immunoenhancing activity are essentially unknown. The aim of our study was to examine whether CLA showed specific effects in vitro on a T cell model, represented by the Jurkat cell line. CLA was found non toxic for Jurkat in the range 50-200 microM, as assessed by LDH release; however, incubation with 50 microM CLA was associated to a significant inhibitory effect on cell proliferation. The analysis of IL-2 and IFN-gamma transcript levels, produced in stimulated Jurkat cells, showed an increased expression of both cytokines in CLA-treated cells. Interestingly, the increased induction of IL-2 but not of IFN-gamma mRNA, could be suppressed by co-incubation with Gö 6976, a protein kinase C (PKC) inhibitor. Co-incubation with superoxide dismutase (SOD) or N-acetyl-L-cysteine (NAC) restored the basal levels of RNA synthesis for both cytokines. Taken together, these results suggest a specific role for dietary CLA in the modulation of the immune response in a T cell line model that is mediated, at least in part, by PKC and through the production of oxidative molecules.