Induction of apoptosis and apoptotic mediators in Balb/C splenic lymphocytes by dietary n-3 and n-6 fatty acids

The present study was designed to investigate the effect of dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) on anti-CD3 and anti-fas antibody-i nduced apoptosis and its mediators in mouse spleen cells. Nutritionally ade quate semipurified diets containing either 5% w/w corn oil (n-6 PUFA) or fi sh oil (n-3 PUFA) were fed to weanling female Balb/C mice, and 24 wk later mice were sacrificed. In n-3 PUFA-fed mice, serum and splenocyte lipid pero xides were increased by 20 and 28.3% respectively, compared to n-6 PUFA-fed mice. Further, serum vitamin E levels were decreased by 50% in the n-3 PUF A-fed group, whereas higher anti-Fas- and anti-CD3-induced apoptosis (65 an d 66%) and necrosis (17 and 25%), compared to the n-6 PUFA-fed group, were found when measured with Annexin V and propidium iodide staining, respectiv ely. In addition, decreased Bcl-2 and increased Fas-ligand (Fas-L) also wer e observed in the n-3 PUFA-fed group compared to the n-6 PUFA-fed group. No difference in the ratio of splenocyte subsets nor their Fas expression was observed between the n-3 PUFA-fed and n-6 PUFA-fed groups, whereas decreas ed proliferation of splenocytes was found in n-3 PUFA-fed mice compared to n-6 PUFA-fed mice. In conclusion, our results indicate that dietary n-3 PUF A induces higher apoptosis by increasing the generation of lipid peroxides and elevating Fas-L expression along with decreasing Bcl-2 expression. A re duced proliferative response of immune cells also was observed in n-3 PUFA- fed mice.