Submitted on May 1, 2006
Revised on July 5, 2006
Accepted on July 27, 2006
Conjugated linoleic acid enhances glutathione synthesis and attenuates pathological signs in MRL/lpr mice
Paolo Bergamo, Diomira Luongo, Francesco Maurano, Giuseppe Mazzarella, Rosita Stefanile, and Mauro Rossi
Istituto di Scienze dell'Alimentazione (ISA), Consiglio Nazionale delle Ricerche (CNR), Avellino 83100
Corresponding Author: p.bergamo{at}isa.cnr.it
Conjugated Linoleic Acid (CLA), a naturally occurring peroxisome proliferator-activated receptor-gamma (PPAR
) ligand, exhibit proapoptotic, immunomodulatory and anti-cancer properties. In this study, we examined the biological effects of CLA administration in the MRL/MpJ-Faslpr (MRL/lpr) mouse, an animal model of systemic lupus erythematosus (SLE). We found that CLA exerted apparently opposed activities in ex vivo experiments, depending on its concentration: 100
M CLA down-regulated IFN
synthesis and cell proliferation of splenocytes, in association with apoptosis induction and decrease of intracellular thiols (GSH + GSSG); 25
M CLA instead did not significantly influence cell proliferation, but enhanced the expression of gamma-glutamylcysteine ligase catalytic subunit (GCLC) and intracellular GSH concentration. Interestingly, the anti-proliferative effect at 100
M was not inhibited by PPAR
antagonist GW9662. In vivo, CLA administration drastically reduced SLE signs (splenomegaly, auto-antibodies and cytokine synthesis) a condition paralleled by enhancement of GCLC expression and intracellular GSH content. Moreover, CLA administration significantly down-regulated NF
B activity, independently from PPAR
activation and apoptosis induction. In conclusion enhanced GSH content and GCLC expression in CLA-treated mice suggests a novel biochemical mechanism underlying its immunomodulatory activity and the beneficial effects on murine SLE signs.