Tissue specific regulation of transforming growth factor beta by omega-3 lipid-rich krill oil in autoimmune murine lupus

We have previously reported that hybrid New Zealand female mice [(NZBxNZW) F-1 or B/W) fed a diet enriched in omega-3 lipid-rich fish oil vs. omega-6 lipid-rich corn oil show delayed development of autoimmune lupus nephritis and longer life span. The present study was carried out to explore the possible beneficial effects of oil from Antarctic krill (Euphausia superba) as an alternative source of omega-3 lipids. Weanling B/W mice were fed a nutritionally adequate semipurified diet supplemented with either 10% (wt/wt) krill oil (KO) or corn oil (CO). Cross-sectional studies were carried out on kidneys and spleens at 3.5 and 6.5 months of age. Our results indicate that KO prolonged life span (CO, 266.7 days +/- 12.5; KO, 330.2 days +/- 19.2; P < 0.001) and delayed the onset of proteinuria. Splenocytes from KO mice displayed greater proliferative responses to mitogen (concavalin A), and significantly lower Pgp-1(+) cells in both CD4(+) and CD8(+) T cell subsets. Lipid extracts of splenocytes from KO fed mice revealed higher levels of eicosapentaenoic (20:5 omega-3; EPA) and docosahexaenoic (22:6 omega-3; DHA) acids; EPA suppresses prostaglandin synthesis. Further, Northern blot analysis showed decreased expression of the oncogene c-ras (1.5-fold, P < 0.05) in the spleens of KO fed mice. The expression of transforming growth factor beta 1 (TGF beta 1) was higher in spleen cell extracts (3.5-fold; P < 0.025), but lower in kidney extracts (5.97 fold; P < 0.025) of KO fed mice. The data indicate that dietary supplementation with KO modulates expression of TGF beta in an organ specific manner. In the spleen, TGF beta could be immunosuppressive, whereas its expression in the kidney may be pathological and proinflammatory. In summary, dietary KO, like fish oil, can suppress the development of autoimmune murine lupus, and its effects on inflammatory mediators are organ specific.