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 [(NZBx NZW) 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 l upus nephritis and longer life span. The present study was carried out to explore the possible beneficial effects of oil from Antarctic kril l (Euphausia superba) as an alternative source of omega-3 lipids. Wean ling B/W mice were fed a nutritionally adequate semipurified diet supp lemented with either 10% (wt/wt) krill oil (KO) or corn oil (CO). Cros s-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 delay ed the onset of proteinuria. Splenocytes from KO mice displayed greate r 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 eic osapentaenoic (20:5 omega-3; EPA) and docosahexaenoic (22:6 omega-3; D HA) acids; EPA suppresses prostaglandin synthesis. Further, Northern b lot analysis showed decreased expression of the oncogene c-ras (1.5-fo ld, P < 0.05) in the spleens of KO fed mice. The expression of transfo rming growth factor beta 1 (TGF beta 1) was higher in spleen cell extr acts (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 supplementati on with KO modulates expression of TGF beta in an organ specific manne r. In the spleen, TGF beta could be immunosuppressive, whereas its exp ression in the kidney may be pathological and proinflammatory. In summ ary, dietary KO, like fish oil, can suppress the development of autoim mune murine lupus, and its effects on inflammatory mediators are organ specific.