TY - JOUR
T1 - Differential effects of ω-6 and ω-3 fatty acids on interleukin-2 production and mRNA expression by EL-4.IL-2 cells
AU - Venkatraman, Jaya T.
AU - Chandrasekar, Bysani
AU - Weintraub, Susan T.
AU - Fernandes, Gabriel
N1 - Funding Information:
The authors wish to thank Dr. Carl McGee at State University of New York at Buffalo, for his advice in the statistical analysis of the data. This work was supported by NIH grants ROI AG-03417 and AG-10531.
PY - 1995/9
Y1 - 1995/9
N2 - Our studies with lupus-prone (NZBxNZW)F1 (B/W) female mice have indicated that dietary ω--3 lipids (menhaden oil) significantly extend the life span and delay the onset of autoimmune disease, while ω--6 lipids (corn oil) shorten the life span by accelerating the onset and progression of autoimmune disease, probably by altering the cell and subcellular membrane fatty acid composition. To understand the mechanisms through which ω--6 (linoleic acid, 18:2, and arachidonic acid, 20:4) and ω--3 (eicosapentanoic acid, 20:5, and docosahexanoic acid, 22:6) lipids exert their differential effects, we have studied the effects of these fatty acids in vitro on cell proliferation, peroxidation, interleukin-2 (IL-2) production, IL-2 mRNA levels, and surface IL-2 receptor (IL-2R) expression in an IL-2 producing mouse lymphoma cell line (EL-4.IL-2: EL-4). When EL-4 cells were cultured in the presence of individual ω--6 and ω--3 fatty acids (at a final concentration of 10 μg/mL), the respective fatty acid was found to incorporate into the cells at a significant level, and no adverse effects were noted either on the viability of the cells or on the de novo DNA synthesis. In addition, lipid peroxidation, as measured by the generation of thiobarbituric acid-reactive substances, was significantly higher (P < 0.05) in cells incubated with 20:4ω--6 as compared with control cells (to which no fatty acid was added). Also, 20:4ω--6 significantly inhibited (P < 0.05) IL-2 production when compared with other fatty acids. Northern blot analysis revealed that this inhibition in IL-2 production by 20:4ω--6 was at the gene level, as seen by an inhibition in phorbol-12-myristate-13-acetate induced IL-2 mRNA levels by 20:4ω--6. Compared with saturated fatty acids, both ω--6 and ω--3 lipids induced higher IL-2R surface expression, as seen by flow cytometry. These studies suggest that dietary ω--3 lipids lower membrane lipid peroxidation. and thereby may preserve normal immunological functions that may delay the course of autoimmune disease in B/W mice.
AB - Our studies with lupus-prone (NZBxNZW)F1 (B/W) female mice have indicated that dietary ω--3 lipids (menhaden oil) significantly extend the life span and delay the onset of autoimmune disease, while ω--6 lipids (corn oil) shorten the life span by accelerating the onset and progression of autoimmune disease, probably by altering the cell and subcellular membrane fatty acid composition. To understand the mechanisms through which ω--6 (linoleic acid, 18:2, and arachidonic acid, 20:4) and ω--3 (eicosapentanoic acid, 20:5, and docosahexanoic acid, 22:6) lipids exert their differential effects, we have studied the effects of these fatty acids in vitro on cell proliferation, peroxidation, interleukin-2 (IL-2) production, IL-2 mRNA levels, and surface IL-2 receptor (IL-2R) expression in an IL-2 producing mouse lymphoma cell line (EL-4.IL-2: EL-4). When EL-4 cells were cultured in the presence of individual ω--6 and ω--3 fatty acids (at a final concentration of 10 μg/mL), the respective fatty acid was found to incorporate into the cells at a significant level, and no adverse effects were noted either on the viability of the cells or on the de novo DNA synthesis. In addition, lipid peroxidation, as measured by the generation of thiobarbituric acid-reactive substances, was significantly higher (P < 0.05) in cells incubated with 20:4ω--6 as compared with control cells (to which no fatty acid was added). Also, 20:4ω--6 significantly inhibited (P < 0.05) IL-2 production when compared with other fatty acids. Northern blot analysis revealed that this inhibition in IL-2 production by 20:4ω--6 was at the gene level, as seen by an inhibition in phorbol-12-myristate-13-acetate induced IL-2 mRNA levels by 20:4ω--6. Compared with saturated fatty acids, both ω--6 and ω--3 lipids induced higher IL-2R surface expression, as seen by flow cytometry. These studies suggest that dietary ω--3 lipids lower membrane lipid peroxidation. and thereby may preserve normal immunological functions that may delay the course of autoimmune disease in B/W mice.
KW - EL-4
KW - IL-2 levels
KW - IL-2 mRNA
KW - IL-2R expression
KW - lipid peroxidation
KW - proliferative response
KW - ω-3 tatty acids
KW - ω-6 fatty acids
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U2 - 10.1016/0955-2863(95)00078-E
DO - 10.1016/0955-2863(95)00078-E
M3 - Article
AN - SCOPUS:0028851118
SN - 0955-2863
VL - 6
SP - 467
EP - 473
JO - The Journal of Nutritional Biochemistry
JF - The Journal of Nutritional Biochemistry
IS - 9
ER -