Abstract
Studies from our laboratory indicate that n-3 (fish oil, FO) lipids at 10% (w/w) in a nutritionally adequate, semipurified diet, and supplemented with equal levels of antioxidants, extended the life span of lupus-prone (NZB/NZW)F1 (B/W) female mice as compared to n-6 (corn oil, CO) lipids. The early rise of autoimmune disease in CO-fed mice was closely linked to the loss of T-cell function. Both IL-2 production and IL-2 receptor expression were reduced due to the loss of naive T-Cells and a rise in memory T-cells. Proliferative response to both mitogens and superatigens (staphylococcal enterotoxins A and B) was higher in FO-fed 6.5-mon-old mice. These changes paralleled decreased PGE2 production by splenic cells from FO-fed mice.
Analysis of mRNA expression in different organs revealed differential effects of dietary lipids. In FO-fed, mice, transforming growth factor β1 (TGF β1) expression was decreased in kidneys, but splenic tissues had higher expression of TGF β mRNA. As TGF β promotes programmed cell death (PCD), we studied the effects of CO and FO on PCD rates in lymphocytes. Both propidium iodide staining and DNA fragmentation were elevated in lymphocytes of FO-fed mice when compared to CO-fed mice of similar age. Also, increased PCD correlated closely with increased Fas gene expression. Thus, in addition to various other antiinflammatory effects, dietary FO appears to increase PCD and prevent accumulation of self-reactive immune cells in lymphoid organs. Further studies are required to dissect the proand antiinflammatory mechanisms associated with dietary n-3 and n-6 lipids in modulating autoimmune disorders or malignancy during aging.
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Abbreviations
- B/W mice:
-
(NZB/NZW)F1 mice
- CAT:
-
catalase
- CO:
-
corn oil
- CTLL-2:
-
cytotoxic T-lymphocyte line 2
- FACS:
-
fluorescence activated cell sorting
- FO:
-
fish oil
- GSH-Px:
-
glutathione peroxidase
- ICAM-1:
-
intercellular adhesion molecule-1
- IL-2:
-
interleukin-2
- LTB4 :
-
luekotriene B4
- MDA:
-
malondialdehyde
- MRL/lpr mice:
-
MRL mouse with a lymphoroliferative (lpr) gene
- PCD:
-
programmed cell death
- PGE2 :
-
prostaglandin E2
- PI:
-
propidium iodide
- SLE:
-
systemic lupus erythematosus
- SOD:
-
superoxide dismutase
- TBARS:
-
thiobarbituric acid-reactive substances
- TBHQ:
-
tert-butylhydroquinone
- TGF β:
-
transforming growth factor β
- TNF-α:
-
tumor necrosis factor-α
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Fernandes, G., Chandrasekar, B., Luan, X. et al. Modulation of antioxidant enzymes and programmed cell death by n-3 fatty acids. Lipids 31, S91–S96 (1996). https://doi.org/10.1007/BF02637058
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DOI: https://doi.org/10.1007/BF02637058