DIETARY OMEGA-3 LIPIDS DELAY THE ONSET AND PROGRESSION OF AUTOIMMUNE LUPUS NEPHRITIS BY INHIBITING TRANSFORMING GROWTH-FACTOR-BETA MESSENGER-RNA AND PROTEIN EXPRESSION

The present study was carried out to test whether transforming growth factor beta (TGF-beta) plays a pathological role in the induction or p rogression of glomerulonephritis in a murine model of systemic lupus e rythematosus (SLE), and whether dietary supplementation with fish oil (FO) can modulate the expression of TGF beta. Weanling female (NZB x N ZW) F-1 (BNCT) mice were divided into three groups. One group was fed an unmanipulated diet (lab. chow; LC) and the other two groups were fe d a nutritionally adequate semipurified diet supplemented with 10% CO or FO. Bath water and food were provided ad libitum. Proteinuria and s erum anti-dsDNA antibody levels were measured to assess disease progre ssion. Mice were killed at 3.5 and 6.5 months of age and renal mRNA le vels for TGF beta isoforms, fibronectin-1 (FN-1) and intercellular adh esion molecule-1 (ICAM-1) were studied by Northern blot analysis. TGF beta 1 protein levels were also examined in kidneys by Western blot an alysis. Our results indicate that at 3.5 months of age, when urinary p rotein levels were undetectable and very low levels of anti-dsDNA were detected, no mRNA signal could be detected for TGF beta isoforms, ICA M-1 and FN-1 in either dietary group. However, at 6.5 months, the FO-f ed mice, compared to LC and CO, had [1] greatly reduced proteinuria (L C: 2-3+, CO: 2-3+; FO: trace -1+) and serum anti-dsDNA antibodies; [2] improved survival (GO: 100%) death (15/15) occurred by 8 months; FO: 50% were alive at 12 months (8/15) and [3] reduced renal TGF beta 1 mR NA and protein levels. TGF beta 2 and beta 3 were not significantly af fected by FO diet. Similarly, lower levels of renal FN-1 and ICAM-1 mR NA were observed in FO fed mice. These data indicate that in B/W mice on a FO diet, prolonged survival and amelioration of renal disease may be attributed at least in part to lower levels of TGF beta 1 mRNA and protein in the kidneys.